Combined immunodeficiency: Difference between revisions

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Overview
Classification
Immunodeficiency Affecting Cellular and Humoral Immunity
Combined Immunodeficiency
Predominantly Antibody Deficiency
Diseases of Immune Dysregulation
Congenital Defects of Phagocytes
Defects in Intrinsic and Innate Immunity
Auto-inflammatory Disorders
Complement Deficiencies
Phenocopies of Primary Immunodeficiency

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Latest revision as of 23:01, 28 January 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[3]; Anum Gull M.B.B.S.[4]; Farman Khan, MD, MRCP [5]; Sadaf Sharfaei M.D.[6]

Overview

Please see Common variable immunodeficiency. There are a variety of syndromic conditions related to immunodeficiency. Some syndromic conditions are inherited.

Classification

Combined Immunodeficiency Diseases with associated or syndromic features

Congenital thromocytopenia

DNA Repair Defects

Immuno-osseous dysplasias

Thymic Defects with additional congenital anomalies

Hyper-IgE syndromes(HIES)

Dyskeratosis congenita (DKC)

Defects of Vitamin B12 and Folate metabolism

Anhidrotic Ectodermodysplasia with ID

Others

Wiskott Aldrich Syndrome

Ataxia telangiectasia

Cartilage Hair Hypoplasia

DiDeorge Syndrome

Job Syndrome

Dyskeratosis congenita

Transcobalmin 2 deficiency

NEMO deficiency

Purine nucleoside phosphorylase deficiency

XL thrombocytopenia

Nijmegen breakage Syndrome

Schimke Syndrome

TBX1 deficiency

Comel Netherton Syndrome

COATS plus syndrome

Deficiency causing hereditary folate malabsorption

EDA-ID due to IKBA GOF mutation

ID with multiple intestinal atresias

WIP deficiency

Bloom syndrome

MYSM1 deficiency

Chromosome 10p13-p14 deletion Syndrome

PGM3 deficiency

SAMD9

Methylene-tetrahydrofolate-dehydrogenase 1 deficiency

Hepatic veno-occlusive disease with immunodeficiency

ARPC1B deficiency

PMS2 deficiency

MOPD1 deficiency

CHARGE Syndrome

SAMD9L

Vici Syndrome

Immunodeficiency with centromeric instability and facial anomalies(ICF1, ICF2, ICF3, ICF4)

EXTL3 deficiency

HOIL1 deficiency, HOIP1 deficiency

MCM4 deficiency

Calcium Channel Defects(ORAI-1 deficiency, STIM1 deficiency)

RNF168 deficiency

Hennekam-lymphangiectasia-lymphedema syndrome

POLE1 deficiency

STAT5b deficiency

POLE2 deficiency

Kabuki Syndrome

NSMCE3 deficiency

ERCC6L2(Hebo deficiency)

Ligase 1 deficiency

GINS1 deficiency

Wiskott-Aldrich Syndrome

Wiskott Aldrich syndrome (WAS) is X-Linked recessive primary immunodeficiency disorder.
The classic triad of Wiskott-Aldrich syndrome include followings:^[1]
- Eczema
- Thrombocytopenia
- Recurrent infections
WAS gene which helps in actin polymerization, signal transduction and cytoskeletal rearrangement.^[2]^[3]
The only curative treatment for Wiskott-Aldrich syndrome is stem cell transplant.^[4]

X-linked thrombocytopenia (XLT)

X-Liked thrombocytopenia is a less severe variant of wiskot aldrich syndrome.
X-Liked thrombocytopenia presents as a benign disease with good long-term survival compared with classic WAS.^[5]^[6]^[7]
There is a relationship between XLT and WAS as both are caused by mutations of the same gene.^[8]
WAS gene is mutated in X linked thrombocytopenia .^[8]
X linked thrombocytopenia is inherited as a X- linked-recessive pattern.
X linked thrombocytopenia is characterized by:
- Mild-to-moderate eczema
- Mild infrequent infections
- Small-sized platelets

Treatment for patients with XLT is still not determined.^[5]

WIP Deficiency

WIPF1 gene which is located on chromosome 2q31.1

Mutation of WIPF1 gene leads to WIP deficiency.

WASP is totally complexed with the WASP-interacting protein (WIP).^[9]
Deficiency of WIP leads to autosomal recessive form of Wiskott Aldrich syndrome.
A main function of WIP is to stabilize WASP and prevents its degradation.
WASP protein levels are greatly reduced in T lymphocytes.^[10]
The presentation is similar to Wiskott-Aldrich syndrome which includes followings:
Immunologic analysis shows decreased numbers of B cells and T cells, especialy CD8+ T cells.
Hematopoietic stem cell transplantation is the treatment of choice.^[11]

ARPC1B Deficiency

ARPC1B is inherited as an autosomal recessive disorder.
ARPC1B also known as actin-related protein 2/3 complex, subunit 1B which is located on 7q22.1.
The human complex consists of 7 subunits, including the actin-related proteins ARP2 and ARP3.
ARPC1B complex is involved in the control of actin polymerization in cells.^[12]
Deficiency of ARPC1B complex leads to platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.^[13]
Severe manisfestations of ARPC1B deficiency include followings: ^[14]
Less severe manisfestations include mild vasculitis and normal numbers of small platelets without severe infections.
Laboratory studies show platelets with an abnormal shape and decreased dense granules.
Levels of eosinophils, B-lymphocytes, IgA and IgE are increased due to immune dysregulations.^[15]

Ataxia-telangietectasia

Ataxia-telangiectasia (AT) is an autosomal recessive disorder caused by defective ATM gene.
The ATM gene is located on chromosome 11q22.3.
ATM gene is involved in cell responses to DNA damage and cell cycle control.^[16]
Common manifestations of AT include followings:^[17]^[18]^[19]^[20]
- Neurologic abnormalities
  - Progressive cerebellar ataxia
  - Abnormal eye movements
  - Oculomotor apraxia
  - Mild to moderate cognitive impairment
  - Choreoathetosis
- Dermatologic manifestations
  - Telangiectasias on exposed areas including pinnae, nose, face, and neck
  - Hypopigmented macules
  - Melanocytic nevi
  - Facial papulosquamous rash
- Oculocutaneous Telangiectasia
- Pulmonary disease
  - Recurrent sinopulmonary infections
  - Bronchiectasis
  - Interstitial lung disease
  - Pulmonary fibrosis
- Neuromuscular abnormalities
  - Dysphagia
  - Aspiration
  - Respiratory muscle weakness
Diagnostic criteria for ataxia-telangiectasia includes followings:^[21]^[22]^[23]
- Definitive diagnosis
  - Increased radiation-induced chromosomal breakage in cultured cells
  - Progressive cerebellar ataxia and who has disabling mutations on both alleles of ATM
- Probable diagnosis
  - Ocular or facial telangiectasia
  - Serum IgA at least 2 SD below normal for age
  - Alpha fetoprotein at least 2 SD above normal for age
  - Increased radiation-induced chromosomal breakage in cultured cells
Diagnosis can also be made by rapid immunoblotting assay for ATM protein because its levels are greatly reduced.^[22]
It leads to increased risk of development of lymphoid malignancies and immunodeficiency.
Cerebellar atrophy will be seen on MRI or CT scan.

Nijmegen breakage Syndrome

It is also known as Ataxia-telangiectasia variant-1.
Nijmegen breakage syndrome (NBS) is caused by mutation in the NBS1 gene which is located on chromosome 8q21.
It is inherited as an autosomal recessive disorder.
Common manifestations include followings:^[24]^[24]^[25]^[26]
- Microcephaly
- Dysmorphic facial features
- Mild growth retardation
- Mild-to-moderate intellectual disability
- Café-au-lait spots and depigmented skin lesions
- Ovarian dysgenesis and premature ovarian failure in females
- Hypergonadotropic hypogonadism and infertility in males
- Recurrent sinopulmonary infections
A strong predisposed to development of malignancies of lymphoid origin
The patients are also hypersensitive to double stand DNA breaking-inducing agents e.g ionizing radiations.^[27]
There is no specific treatment for NBS.

Bloom Syndrome

Bloom syndrome is also called as Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema.
Bloom syndrome is caused by the mutation in the BLM gene which is located on chromosome 15q26.
BLM gene encodes DNA helicase RecQ protein-like-3 (RECQL3).^[28]^[29]
Bloom Syndrome is inherited as an autosomal recessive inherited disorder.
Most common manifestations of Bloom syndrome include followings:^[30]^[28]
- Growth deficiency of prenatal onset
- Immunodeficiency
- Café-au-lait spots or hypopigmented skin lesions
- Excessive photosensitivity with facial lupus-like skin lesions
- Type 2 diabetes mellitus
- Hypogonadism
- Predisposition to the development of all types of cancers
Bloom syndrome is diagnosed by detecting mutations in BLM gene.^[31]
There is no specific treatment for bloom syndrome.

PMS2 Deficiency

PMS2 also known as Post-Meiotic Segregation 2.

PMS2 gene is located on chromosome 7p22.1

PMS2 gene encodes for DNA repair proteins which are involved in DNA mismatch repair.^[32]

PMS2 Deficiency is inherited as autosomal recessive pattern.^[33]
Deficiency of PMS2 increases the risk of colorectal cancer and hereditary nonpolyposis.^[34]

Immunodeficiency with Centromeric instability and Facial anomalies(ICF1, ICF2, ICF3, ICF4)

ICF2 is caused by mutation in the ZBTB24 gene on chromosome 6q21.^[35]
ICF3 is caused by mutation in the CDCA7 gene on chromosome 2q31.
ICF4 is caused by mutation in the HELLS gene on chromosome 10q23.

It is an autosomal recessive disease.
Common manifestations of ICF include followings:^[36]^[37]
The presenting symptom is recurrent infections usually in early childhood.
At least two immunoglobulin classes are affected in each patient and agammaglobulinemia can occur.
T cell number and response to mitogen may be decreased.^[38]^[39]^[36]
The centromeric instability most frequently involves chromosomes 1 and 16, often 9, and rarely 2 and 10.
The differential diagnosis include Bloom syndrome, ataxia-telangiectasia, and Nijmegen breakage syndrome.
Immunoglobulin should be given in the early phase.^[40]
Severe cases can be treated with allogeneic hematopoietic cell transplantation.^[41]

MCM4 Deficiency

MCM stands for minichromosome maintenance complex component 4. MCM4 is one part of a MCM2-7 complex which functions as the replicative helicase which is essential for normal DNA replication and genome stability.
MCM4 deficiency is caused by mutation in the MCM4 gene located on 8q11.21. ^[42]
MCM4 deficiency is characterized by:^[43]
- Short stature
- Adrenal insufficiency
- NK cell deficiency which leads to recurrent viral illnesses^[44]^[45]
MCM4 deficiency is a variant of familial glucocorticoid deficiency (FGD), an autosomal recessive form of adrenal failure.^[45]
MCM4 deficiency shares biochemical features of familial glucocorticoid deficiency, with isolated glucocorticoid deficiency, increased ACTH, and normal aldosterone and renin levels.
Individuals with adrenal insufficiency should be given corticosteroid replacement therapy.

RNF168 Deficiency

RNF168 stands for Ring finger protein 168(RNF168).
RNF168 gene is located on chromosome 3q29.^[46]
RNF168 gene encodes E3 ubiquitin ligase which is involved in repair of double strand DNA breaks.^[47]
Mutation of RNF168 gene leads to RIDDLE syndrome which is inherited as an autosomal recessive pattern.^[48]
RIDDLE syndrome is characterized by:^[48]
- Radio-sensitivity
- Immunodeficiency
- Dysmorphic features
- Learning difficulties
- Short stature
- Motor control problems
It is pathologically similar to the ataxia-telangiectasia syndrome.^[47]

POLE1 deficiency

POLE1 stands for DNA polymerase, epsilon subunit 1.
The POLE1 gene is located on chromosome 12q24.33.
POLE1 gene encodes the catalytic subunit of DNA polymerase epsilon.
POLE1 deficiency is inherited as an autosomal recessive pattern.
Mutation in the POLE1 leads to FILS syndrome.
The age of onset of FILS syndrome is less than 40 years.^[49]
It is characterized by:
- Facial dysmorphism
- Immunodeficiencies
- Livedo on the skin since birth
- Short stature^[50]^[51]
If the mutation in POLE1 gene is inherited as an autosomal dominant pattern, it leads to colorectal cancer-12 which is characterized by a high predisposition of colorectal adenomas and carcinomas.

POLE2 deficiency

POLE2 stands for DNA polymerase epsilon subunit 2.^[52]
POLE2 gene is located on choromosome 14q21.
POLE2 is involved in both DNA replication and DNA repair.
POLE2 deficiency is inherited as an autosomal recessive pattern.
POLE2 deficiency is characterized by the followings:
- Combined immunodeficiencies
- Facial dysmorphism
- Autoimmunity^[53]

NSMCE3 Deficiency

NSMCE3 stands for non structural maintenance of chromosomes element 3.
NSMCE3 gene is located on chromosome 15q13.1.
NSMCE3 gene encodes a component of the SMC5/SMC6complex.
SMC5/SMC6 complex is important for responses to DNA damage and chromosome segregation during cell division.^[54]
LICS syndrome is inherited as an autosomal recessive pattern.
Mutation in the NSMCE3 gene leads to LICS syndrome.
LICS stands for:
- Lung disease
- Immunodeficiencies
- Chromosome breakage syndrome
Other features include:
- Defective T cells and B cell
- Acute respiratory distress syndrome in early childhood^[55]

ERCC6L2 (Hebo deficiency)

ERCC6L2 gene is located on chromosome 9q22.32.
ERCC6L2 gene belongs to a family of helicases.
ERCC6L2 gene is involved in chromatin unwinding, transcription regulation, DNA recombination, and repair.^[56]
Mutation of ERCC6L2 gene leads to bone marrow failure syndrome 2 which is inherited as an autosomal recessive pattern.^[56]
Bone marrow failure syndrome 2 is characterized by the followings:
- Trilineage bone marrow failure
- Learning disabilities
- Microcephaly^[56]

Ligase 1 Deficiency

LIG1 gene is located on chromosome 19q13.33.
LIG1 gene encodes DNA ligase.
DNA ligase function at the replication fork is to join okazaki fragments during replication of lagging strand DNA.^[57]
Mutation of LIIG1 gene leads to reclassified-variant of unknown significance formerly called as DNA ligase 1 deficiency.
Ligase 1 deficiency is characterized by:
- Immunodeficiency
- Cellular hypersensitivity to DNA-damaging agents^[58]

GINS1 deficiency

GINS1 gene is located on chromosome 20p11.2.
GINS1 gene encodes GINS complex.
GINS1 deficiency is inherited as an autosomal recessive pattern.
GINS1 deficiency is characterized by followings:
- Natural killer cell deficiency
- Chronic neutropenia
- Intrauterine growth retardation
- Mild facial dysmorphism
- Eczematous skin
- Recurrent infections^[59]

Cartilage hair hypoplasia

Cartilage hair hypoplasia is also known as metaphyseal chondroplasia.
Cartilage hair hypoplasia is caused by mutation in the RMRP gene.
RMRP gene is located on chromosome 9p13.
RMRP gene encodes mitochondrial RNA-processing endoribonuclease which is involved in cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA.^[60]^[60]
Cartilage hair hypoplasia is inherited as an autosomal recessive pattern.
Cartilage hair hypoplasia is characterized by the followings:
- Short limbs
- Short stature
- Fine and sparse hair
- Ligamentous laxity
- Defective immunity
- Hypoplastic anemia
- Neuronal dysplasia of the intestine^[61]^[60]
Clinical diagnosis is made by observing fine and sometimes sparse hair in an individual with short stature and disproportionally short limbs.^[62]
Suspected cases of skeletal dysplasia may be evaluated on radiography.
X-ray findings shows metaphyseal ends to be abnormal and appear as scalloped, irregular surfaces that may contain cystic areas.^[63]
Definitive diagnosis is made by genetic analysis of the RMRP gene.

Schimke Immuno-osseous dysplasia (SIOD)

SMARCAL1 gene is located on chromosome 2q25.
SMARCAL1 gene encodes matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1.^[64]^[65]
Homozygous or compound heterozygous mutation of SMARCAL1 gene causes Schimke immuno-osseous dysplasia (SIOD).
Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive disorder.^[64]
It is characterized by:
- Short stature (often with prenatal growth deficiency)
- Spondyloepiphyseal dysplasia
- Defective cellular immunity
- Progressive renal failure
The diagnosis should be considered in patients with short stature and immunodeficiency.
Renal function should be assessed if the diagnosis is suspected.
Radiographs for the characteristic bony anomalies should be performed.
Bone marrow transplantation markedly improved the marrow function.^[66]^[66]

MYSM1 deficiency

MYSM1 gene is located on chromosome 1p32.1.
MYSM1 gene encodes a deubiquitinase which is involved in regulation of trancription and mediates histone deubiquitination.^[67]
MYSM1 deficiency leads to bone marrow failure syndrome 4.
MYSM1 deficiency is inherited as an autosomal recessive pattern.^[68]^[69]
MYSM1 deficiency is associated with:
- Developmental aberrations
- Progressive bone marrow failure with myelodysplastic features
- Increased susceptibility to genotoxic stress
Hematopoietic stem cell transplant is a curative therapy.

MOPD1 deficiency

MOPD1 stands for microcephalic osteodysplastic primordial dwarfism type 1.
MOPD1 deficiency, also known as Taybi-Linder syndrome, caused by mutations of RNU4ATAC gene.
RNU4ATAC gene encodes a small nuclear RNA (snRNA) component of the U12-dependent spliceosome on chromosome 2q14.
MOPD1 deficiency is inherited as an autosomal recessive pattern.^[68]
Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) is characterized by:^[70]
- Intrauterine growth retardation
- Post-natal growth retardation with the following features:
  - Abnormally small head size
  - Abnormal bone growth (skeletal dysplasia)
- Distinctive facial features
- Brain anomalies^[69]
Diagnosis is made on the basis of the clinical and radiological phenotype.
Common radiological features include:
- Short tubular bones
- Enlarged metaphyses
- Vertebral and pelvic anomalies
- Elongated clavicles
- Bowing the long bones
There are no specific treatments for MOPD1 deficiency. There is only supportive therapy.
The prognosis is poor, as most affected individuals die within the first year of life.

EXTL3 deficiency

EXTL3 stands for exostosin-like-glycosyltransferase 3.
EXTL3 gene located on chromosome 8p21.1
EXTL3 regulates the synthesis of heparan sulfate which is important for both skeletal development and hematopoiesis.
Mutation of EXTL3 gene leads to a syndrome called immunoskeletal dysplasia with neurodevelopmental abnormalities.^[71]

Digeorge Syndrome

DiGeorge syndrome is caused by a hemizygous deletion of chromosome 22q11.2 which encodes TBX1 gene.
T-box genes are transcription factors involved in the regulation of developmental processes.
Chromosome 22q11.2 deletion syndrome includes DiGeorge syndrome and other similar syndromes such as velocardiofacial syndrome.
DiGeorge syndrome is inherited as an autosomal dominant pattern.
22q11.2 deletion leads to defective development of the 3rd and 4th pharyngeal pouch system.
DiGeorge syndrome presents with the following:^[72]
- Conotruncal cardiac anomalies
- Hypoplastic thymus
- Hypocalcemia
- Palatal abnormalities
- Developmental delay
- T cell immunodeficiency presents with:
  - Recurrent sinopulmonary infections
  - Severe combined immunodeficiency
Any neonate with a conotruncal heart lesion, hypocalcemia or cleft palate should be evaluated for DiGeorge syndrome.^[73]
DiGeorge syndrome is diagnosed by decreased numbers of CD3+ T cells, combined with either characteristic clinical findings or deletion in chromosome 22q11.2.
T cell receptor excision circles (TRECS), a biomarker of T cell development is also used to made by diagnosis during newborn screening.^[74]
DiGeorge syndrome should be treated with supplementation of vitamin D or calcium and with parathyroid hormone.
Hematopoietic stem cell transplantation is the definitive treatment.^[75]

TBX1 deficiency

T-box transcription factor, TBX1 gene, also known as T-box protein 1 is located on chromosome 22q11.21.
Genes in the T-box family play important roles in the formation of tissues and organs during embryonic development.
Mutations in the TBX1 gene leads to conotruncal anamoly face syndrome and velocardiofacial syndrome.

Chromosome 10p13-p14 deletion Syndrome

Chromosome 10p13-p14 deletion syndrome is a rare disease in which the end portion of the short arm (p) of chromosome 10 is missing.
The severity of symptoms is variable, depending upon the exact size or location of the deletion on chromosome 10p.
Clinical features often include followings:
- Severe mental retardation
- Postnatal growth retardation resulting in short stature
- Distinctive malformations of the skull and craniofacial region
- A short neck
- Congenital heart defects
Affected individuals have some features of DiGeorge syndrome.
Chromosome 10p13-p14 deletion syndrome is diagnosed prenatally by tests such as amniocentesis or chorionic villus sampling.
The treatment of affected individuals is symptomatic and supportive.

CHARGE Syndrome

CHARGE syndrome is caused by heterozygous mutation in the CHD7 gene located on chromosome 8q12.
CHARGE Syndrome is inherited as an autosomal dominant pattern.
CHD7 gene is essential for the formation of multipotent migratory neural crest cells. Neural crest cells are ectodermal in origin, but undergo a major transcriptional reprogramming event and acquire a differentiation potential and ability to migrate throughout the body.
CHARGE syndrome stands for:^[76]^[77]
- Coloboma
- Heart anamoly
- Choanal atresia
- Retardation
- Genital anamolies
- Ear anamolies

Job Syndrome

STAT3 gene stands for signal transducer and activator of transcription 3.
STAT3 gene is important in the JAK-STAT signaling pathway activated by cytokines such as IL-6 and IL-2.
Defects in the JAK-STAT pathway also lead to impaired T helper cell type 17 (Th17) differentiation and function.
Defect in Th17 cells function also results in decreased neutrophil proliferation and chemotaxis to the site of infection.
Job syndrome, also known as Hyper-IgE syndrome, is caused by heterozygous mutation in the STAT3 gene on chromosome 17q21.
Job syndrome is inherited as autosomal dominant pattern.
Job syndrome is characterized by the following:
- Chronic eczema
- Recurrent staphylococcal infections resulthing in cold abcess
- Increased serum IgE
- Eosinophilia
- Skeletal manifestation such as:
  - Distinctive coarse facial appearance
  - Abnormal dentition
  - Hyperextensibility of the joints
  - Bone fractures
The diagnosis of job syndrome is based upon the presence of suggestive clinical and laboratory findings, and confirmed by molecular testing of STAT3 gene.
Management of jobs syndrome is focused on skin care and antimicrobial prophylaxis.

Comel Netherton syndrome

Comel Netherton syndrome is caused by mutations in the serine protease inhibitor of Kazal type 5 gene (SPINK5) on chromosome 5q32.
SPINK5 gene encodes a multidomain serine protein kinase known as lymphoepithelial Kazal type inhibitor (LEKTI) expressed in epithelial and mucosal surfaces.^[78]
Lymphoepithelial Kazal type inhibitor directly inhibits kallikreins, especially kallikrein 5 (KLK5).
Kallikreins are critical epidermal proteases and essential for regulating skin desquamation.
Comel Netherton syndrome is inherited as an autosomal recessive pattern.
Comel Netherton syndrome is clinically characterized by the followings:^[79]
- Congenital ichthyosiform erythroderma
- Astrichorrhexis invaginata ("bamboo hair")
- Atopic diathesis
Comel Netherton syndrome patients exhibit absent LEKTI staining in the epidermis.
Genetic testing will identify a germline SPINK5 mutation and confirm the diagnosis in approximately 66 to 75 percent of cases.^[80]
There is no specific therapy for Comel Netherton syndrome. It is mainly supportive.

PGM3 deficiency

PGM 3 stands for phosphoglucomutase3.
PGM3 gene is located on chromosome 6q14.
Mutation of PGM3 gene leads to immunodeficiency-23 (IMD23).^[81]
PGM3 deficiency is inherited as an autosomal recessive.
PGM3 deficiency, also known as immunodeficiency-vasculitis-myoclonus syndrome, is characterized by the following:^[82]^[81]
- Recurrent respiratory and skin infections beginning in early childhood
- Developmental delay
- Cognitive impairment of varying severity
- Eczema
- Increased serum IgE

Dyskeratosis congenita

Dyskeratosis congenita is caused by mutation in DKC1 gene on chromosome Xq28.^[83]
DKC1 gene maintains telomere length in rapidly dividing cells.
Mutations in DKC1 gene lead to premature cell death and senescence.^[84]
Dyskeratosis congenita is inherited as an X-linked recessive disorder.
Dyskeratosis congenita is characterized by the following:^[85]
- Abnormal skin pigmentation
- Nail dystrophy
- Leukoplakia of the oral mucosa

COATS plus syndrome

COATS plus syndrome is also known as cerebroretinal microangiopathy with calcifications and cysts-1.
COATS plus syndrome is caused by mutation in the CTC1 gene on chromosome 17p13.
COATS plus syndrome is inherited as an autosomal recessive pattern.
COATS plus syndrome is characterized by followings:^[86]
- Retinal telangiectasias with exudates
- Intracranial calcifications
- Cerebellar movement disorder
- Osteopenia
- Leukoencephalopathy
- Poor growth
- Bone marrow failure

SAMD9 Mutation

SAMD9 gene stands for sterile alpha motif domain-containing protein 9.
SAMD9 gene located on 7q21.2.
SAMD9 gene is encodes a protein which is localized in cytoplasm and involved in regulating cell proliferation and apoptosis.
Mutation of SAMD9 gene leads to MIRAGE syndrome.
MIRAGE syndrome is inherited as an autosomal dominant pattern.
MIRAGE syndrome is form of syndromic adrenal hypoplasia characterized by the following:^[87]
- Myelodysplasia
- Infection
- Restriction of growth
- Adrenal hypoplasia
- Genital phenotypes
- Enteropathy
MIRAGE syndrome is often fatal within the first decade of life as a result of invasive infection.
If the mutation is SAMD9 gene is inherited as an autosomal recessive pattern, it leads to familial tumoral calcinosis
Familial tumoral calcinosis is characterized by massive periarticular and visceral deposition of calcified tumors.^[88]

SAMD9L Mutation

SAMD9L stands for sterile alpha motif domain containing protein 9-like.
SAMD9L gene is located on chromosome 7q21.2.
Mutation of SAMD9L gene leads to ataxia-pancytopenia syndrome.^[89]
Ataxia-pancytopenia syndrome is inherited as an autosomal dominant pattern.^[89]
Ataxia-pancytopenia syndrome is characterized by the following:
- Cerebellar ataxia
- Variable hematologic cytopenias
- Bone marrow failure
- Myeloid leukemia

Transcobalmin 2 deficiency

Transcobalmin 2 deficiency is caused by mutation in TCN2 gene.
TCN2 gene is located on chromosome 22q12.2.
The TCN2 gene encodes transcobalamin II which is a plasma globulin that acts as the primary transport protein for vitamin B12.
Transcobalmin 2 is also called as vitamin B12 binding protein 2.
Transcobalamin 2, as well as intrinsic factor, is required for transportation of cobalamin from the intestine to the blood.
Transcobalmin 2 deficiency is inherited as an autosomal recessive pattern.
Transcobalmin 2 deficiency is characterized by the following:^[90]
- Failure to thrive
- Megaloblastic anemia
- Pancytopenia
- Methylmalonic aciduria
- Recurrent infections
- Mental retardation
- Neurologic abnormalities
Definitive treatment is cobalamin supplement.

Hereditary Folate Malabsorption

Hereditary folate malabsorption is caused by mutation of SLC46A1 gene.
SLC46A1 gene is located on chromosome 17q11.
Hereditary folate malabsorption is an autosomal recessive disorder.
Hereditary folate malabsorption leads to impaired intestinal folate absorption and impaired transport of folate into the central nervous system.
Hereditary folate malabsorption presents in infancy and characterized by signs and symptoms of folate deficiency.
Hereditary folate malabsorption presents by the following features:^[91]
- Low blood and cerebrospinal fluid folate levels
- Megaloblastic anemia
- Diarrhea
- Immunodeficiency
- Infections
- Neurologic deficits
Definitive treatment is folate supplementation.

MTHFD1 deficiency

The MTHFD1 gene encodes a trifunctional protein comprising 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase.
These 3 sequential enzymes are involved in the interconversion of 1-carbon derivatives of tetrahydrofolate (THF) which are substrates for methionine, thymidylate, and de novo purine synthesis.
Mutation of MTHFD1 gene leads to combined immunodeficiency and megaloblastic anemia with or without increased homocysteinemia.^[92]
The MTHFD1 deficiency is inherited as an autosomal recessive disorder.^[93]
The deficiency is characterized by the following:
- Hemolytic uremic syndrome
- Macrocytosis
- Epilepsy
- Hearing loss
- Retinopathy
- Mild mental retardation
- Lymphopenia
- Low T-cell receptor excision circle
MTHFD1 deficiency is treated by folinic acid and hydroxycobalamin supplementation.

NEMO deficiency

NEMO stands for NF-kappa-B essential modifier.
NEMO is encoded by a IKBKG gene on the X chromosome.
NEMO also known as IKBKG gene (inhibitor of kappa polypeptide gene enhancer kinase gamma).^[94]
IKBKG belongs to a family of NEMO-like kinases that function in numerous cell signaling pathways.
NEMO-like kinases specifically phosphorylate serine or threonine residues that are followed by a proline residue.
Ectodermal dysplasia and immune deficiency-1 (EDAID1) is caused by mutation in the IKK-gamma gene (IKBKG or NEMO )on Xq28.
NEMO deficiency is inherited as an X-linked recessive disorder.
NEMO deficiency is characterized by ectodermal dysplasia with combined immunodeficiencies.^[95]

EDA-ID due to IKBA GOF mutation

Mutations in the NFKBIA gene result in functional impairment of NFKB , a master transcription factor required for normal activation of immune responses.
Interruption of NFKB signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection.
Ectodermal dysplasia and immune deficiency-2 (EDAID2) is caused by heterozygous mutation in the NFKBIA gene on chromosome 14q13.
It is inherited as an autosomal dominant pattern
EDAID2 is characterized by variable features of ectodermal dysplasia e.g.hypo/anhidrosis, sparse hair, tooth anomalies) and various immunologic and infectious phenotypes of differing severity.

Purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase deficiency is caused by mutation in the PNP gene.
Purine nucleoside phosphorylase is one of the enzymes of purine salvage pathway.
Defects in purine nucleoside phosphorylase enzyme lead to intracellular accumulation of metabolites that incldes deoxyguanosine triphosphate (dGTP).
Deoxyguanosine triphosphate is particularly toxic to T cells.^[96]
Purine nucleoside phosphorylase deficiency is autosomal recessive disorder.
Purine nucleoside phosphorylase deficiency is characterized mainly by decreased T-cell function.
Patients typically present in infancy to early childhood with frequent bacterial, viral, and opportunistic infections.^[97]
Purine nucleoside phosphorylase deficiency also presents with progressive neurologic symptoms which includes ataxia, developmental delay and spasticity
Low serum uric acid associated with T cell deficiency is highly suggestive of PNP deficiency.
Diagnosis of purine nucleoside phosphorylase deficiency is confirmed by measurement of PNP enzyme activity.
The only curative procedure for PNP deficiency is a hematopoietic stem cell transplantation.

ID with multiple intestinal atresias

Also known as familial intestinal polyaterisa syndrome.
Mutation in the TTC7A gene leads to gastrointestinal defects and immunodeficiency syndrome.
TTC7A gene is located on chromosome 2p21.
TT7CA stands for tetratricopeptide repeat domain 7A.
TTC7A protein involves in proper development andfunction of both thymic and GI epithelium.^[98]
Gastrointestinal defects and immunodeficiency syndrome is inherited as an autosomal recessive inheritance.
Gastrointestinal defects and immunodeficiency syndrome is characterized by followings
- Multiple intestinal atresia, in which atresia throughout intestines.^[99]
- Combined immunodeficiency
Surgical outcomes are poor, and the condition is usually fatal within the first month of life.

Hepatic veno-occlusive disease with immunodeficiency

Hepatic venoocclusive disease with immunodeficiency is caused by mutation in the SP110 gene.
SP110 gene is located on chromosome 2q37.
SP10 gene encodes a protein called SP110 nuclear body protein which is involved in immuni reguation.
Hepatic venoocclusive disease with immunodeficiency is an autosomal recessive disorder.
Hepatic venoocclusive disease is associated with hepatic vascular occlusion and fibrosis.
The immunodeficiency in hepatic venoocclusive disease is characterized by followings:^[100]
- Severe hypogammaglobulinemia
- Combined T and B cell immunodeficiency
- Absent lymph node germinal centers
- Absent plasma cells
Hepatic veno-occlusive disease should be treat with intravenous immunoglobulin and pneumocystis jerovici prophylaxis.

Vici Syndrome

Vici syndrome is caused by mutation in the EPG5 gene.
EPG5 gene is located on chromosome 18q.
EPG5 encodes a gene called EPG5 which stands for ectopic P-granules autophagy protein 5.
Ectopic P-granules autophagy protein 5 a key regulator in autophagy and forms autolysosomesrome.^[101]
Vici syndrome is inherited as an autosomal recessive pattern.^[102]
Vici syndrome is characterized by followings:^[103]
- Agenesis of the corpus callosum
- Cataracts
- Pigmentary defects
- Progressive cardiomyopathy
- Variable immunodeficiency
- Profound psychomotor retardation
- Hypotonia due to a myopathy

HOIL1 deficiency

HOIL1 stands for heme -oxidized IRP2 ubiquitin ligase 1.
HOIL1 also RBCK1 gene.
RBCK1 gene encodes 1 of the components of the linear ubiquitin chain assembly complex(LUBAC)
RBCK1 gene is located on chromosome 20p13
Mutation in the RBCK1 leads to polyglucosan body myopathy.
Polyglucosan body myopathy is inherited as autosomal recessive disorder.^[104]
Polyglucosan body myopathy-1 is characterized by progressive proximal muscle weakness in early childhood.^[105]
Most patients with polyglucosan body myopathy-1 also develop progressive dilated cardiomyopathy.
Some patients with polyglucosan body myopathy also presents with severe immunodeficiency.

HOIP1 deficiency

HOIP stands for Hoil 1-Interacting Protein.
HOIP1 deficiency is caused by the mutation in RNF31 gene.
RNF31 gene is located chromosome 14q11.2.
HOIP deficincy is characterized by followings:^[105]
- Multiorgan autoinflammation
- Combined immunodeficiency
- Subclinical amylopectinosis
- Systemic lymphangiectasia

Calcium Channel Defects (ORAI-1 deficiency)

ORAI1 is also known as calcium release-activated calcium modulator1 (CRAMC1).
ORAI1 gene is located on chromosome 12q24.
ORAI1 (CRAMC1) gene encodes a plasma membrane protein essential for pore-forming subunit of the Ca2+ release-activated calcium channels.
Mutation in the ORAI1 gene leads to primary immunodeficiency-9.^[106]
Primary immunodeficiency-9 in inherited as an autosomal recessive disorder.
Common manifestations of calcium channel defects include followings:
- Recurrent infections due to defective T-cell activation
- Congenital myopathy
- Muscle weakness
- Ectodermal dysplasia including soft dental enamel
If the mutation in the ORAI1 gene is inherited as an autosomal dominant pattern it leads to tubular aggregate myopathy-2.^[107]
Tubular aggregate myopathy-2 is characterized by muscle pain, cramping, or weakness that begins in childhood and worsens over time.^[108]
Tubular aggregate myopathy-2 involves build up of proteins abnormally in both type I and type II muscle fibers and forms clumps of tube-like structures called tubular aggregates

STIM1 deficiency

STM1 stands for stromal interaction molecule 1.
STIM1 gene is located on chromosome 11p15.
STIM1 gene encode stromal interaction molecule 1
Stromal interaction molecule1 senses release of Ca2+ from endoplasmic reticulum and activates CRAC channels in the plasma membrane.
Mutation in the STIM1 gene leads to primary immunodeficiency-10.^[109]
Immunodeficiency-10 is iherited as an autosomal recessive disorder.^[110]
Immunodeficiency-10 is characterized by recurrent infections in childhood due to defective T- and NK-cell function.
Immunodeficiency-10 also have followigs:
- Hypotonia
- Hypohidrosis
- Dental enamel hypoplasia consistent with amelogenesis imperfecta

Hennekam-lymphangiectasia-lymphedema syndrome 2

Hennekam lymphangiectasia-lymphedema syndrome-2 is caused by mutation in the FAT4 gene on chromosome 4q28.
Hennekam lymphangiectasia-lymphedema syndrome-2 is inherited as an autosomal recessive pattern.^[111]
FAT4 gene encodes a protein which is a member of a large family of protocadherins.
Hennekam-lymphangiectasia-lymphedema syndrome 2 is characterized by followigs:
- Generalized lymphatic dysplasia
- Facial dysmorphism
- Cognitive impairment.^[111]

STAT5b deficiency

STAT5b deficiency also known as signal transducer and activator of transcription 5B.^[112]
STAT5 proteins are components of the common growth hormone and interleukin-2 families of cytokines signaling pathway.
STAT family members are phosphorylated by the receptor associated kinases in response to cytokines and growth factors.
STAT proteins then form homo-or heterodimers that translocate to the cell nucleus where they act as transcription activators.^[113]
Growth hormone insensitivity is caused by a mutation in the STAT5B gene which is required for normal signaling of the GH receptor.^[114]
Growth hormone insensitivity includes the followings:
- Severe growth failure
- Elevated serum concentrations of GH
- Clinical phenotype that identical to congenital GH deficiency.^[115]

Kabuki Syndrome

Kabuki syndrome-1 (KABUK1) is caused by heterozygous mutation in the MLL2 gene (KMT2D).
MLL2 gene (KMT2D) encodes histone methyltransferase which methylates the Lys-4 position of histone H3.
It usually inherits as an autosomal dominant pattern.
Common manifestations of Kabuki syndrome include:^[116]^[117]^[118]
- Congenital mental retardation syndrome
- Postnatal dwarfism
- long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form)
- Broad and depressed nasal tip
- Large prominent earlobes
- Cleft or high-arched palate
- Scoliosis
- Short fifth finger
- Persistence of fingerpads
- Radiographic abnormalities of the vertebrae, hands, and hip joints
- Recurrent otitis media in infancy

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@@ Line 2: / Line 2: @@
 {{ID}}
+{{CMG}} {{shyam}}; {{AE}} {{Akram}}; {{Anum}}; {{FK}}; {{SSH}}
-{{CMG}}; {{AE}} {{Akram}},{{Anum}}
+==Overview==
-==Overview==
+Please see [[Common variable immunodeficiency]]. There are a variety of syndromic conditions related to immunodeficiency. Some syndromic conditions are inherited.
 ==Classification==
-<div style="width: 80%; font-size: 85%;">
 {{Family tree/start}}
 {{Family tree | | | | | | | | | | | | | | | | | | | | | | A01 | | | | | | | | | |A01=Combined Immunodeficiency Diseases with associated or syndromic features}}
@@ Line 40: / Line 40: @@
 {{Family tree | | | | | | |`| D13 | | | | | | | | | | | | | | | | | | | | | |D13=GINS1 deficiency}}
 {{Family tree/end}}
-</div>
 ==Wiskott-Aldrich Syndrome==
-* Wiskott–Aldrich syndrome (WAS) is a rare X-linked Recessive primary [[immunodeficiency]] disorder characterized by the triad of eczema, [[microthrombocytopenia]], and often recurrent infections caused by mutation of WASp gene.<ref name="pmid24817816">{{cite journal |vauthors=Buchbinder D, Nugent DJ, Fillipovich AH |title=Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments |journal=Appl Clin Genet |volume=7 |issue= |pages=55–66 |date=2014 |pmid=24817816 |pmc=4012343 |doi=10.2147/TACG.S58444 |url=}}</ref>
+* [[Wiskott-Aldrich syndrome|Wiskott Aldrich syndrome]] (WAS) is X-Linked [[recessive]] primary [[immunodeficiency]] disorder.
+*The classic triad of Wiskott-Aldrich syndrome include followings:<ref name="pmid7996359">{{cite journal |vauthors=Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA |title=A multiinstitutional survey of the Wiskott-Aldrich syndrome |journal=J. Pediatr. |volume=125 |issue=6 Pt 1 |pages=876–85 |date=December 1994 |pmid=7996359 |doi= |url=}}</ref>
+**[[Eczema]]
+**[[Thrombocytopenia]]
+**Recurrent infections
+* WAS gene which helps in actin [[polymerization]], signal transduction and [[cytoskeletal]] rearrangement.<ref>{{cite journal |vauthors=Buchbinder D, Nugent DJ, Fillipovich AH |title=Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments |journal=Appl Clin Genet |volume=7 |issue= |pages=55–66 |date=2014 |pmid=24817816 |pmc=4012343 |doi=10.2147/TACG.S58444 |url=}}</ref><ref name="pmid24817816">{{cite journal |vauthors=Buchbinder D, Nugent DJ, Fillipovich AH |title=Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments |journal=Appl Clin Genet |volume=7 |issue= |pages=55–66 |date=2014 |pmid=24817816 |pmc=4012343 |doi=10.2147/TACG.S58444 |url=}}</ref>
+*The only curative treatment for [[Wiskott-Aldrich syndrome]] is [[stem cell transplant]].<ref>{{cite journal |vauthors=Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M |title=Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) |journal=Pediatr Hematol Oncol |volume=24 |issue=6 |pages=393–402 |date=September 2007 |pmid=17710656 |doi=10.1080/08880010701454404 |url=}}</ref>
-*WASp is involved in actin [[polymerization]] and associated coupling of [[receptor]] engagement, signaling events, and [[cytoskeletal]] rearrangement.<ref>{{cite journal |vauthors=Buchbinder D, Nugent DJ, Fillipovich AH |title=Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments |journal=Appl Clin Genet |volume=7 |issue= |pages=55–66 |date=2014 |pmid=24817816 |pmc=4012343 |doi=10.2147/TACG.S58444 |url=}}</ref>
+== X-linked thrombocytopenia (XLT) ==
-*Allogeneic [[stem cell]] transplantation is the only curative treatment for Wiskott-Aldrich syndrome.<ref>{{cite journal |vauthors=Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M |title=Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) |journal=Pediatr Hematol Oncol |volume=24 |issue=6 |pages=393–402 |date=September 2007 |pmid=17710656 |doi=10.1080/08880010701454404 |url=}}</ref>
+*X-Liked [[thrombocytopenia]] is a less severe variant of wiskot aldrich syndrome.
+* X-Liked [[thrombocytopenia]] presents as a benign disease with good long-term survival compared with classic WAS.<ref name="pmid20173115">{{cite journal |vauthors=Albert MH, Bittner TC, Nonoyama S, Notarangelo LD, Burns S, Imai K, Espanol T, Fasth A, Pellier I, Strauss G, Morio T, Gathmann B, Noordzij JG, Fillat C, Hoenig M, Nathrath M, Meindl A, Pagel P, Wintergerst U, Fischer A, Thrasher AJ, Belohradsky BH, Ochs HD |title=X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options |journal=Blood |volume=115 |issue=16 |pages=3231–8 |date=April 2010 |pmid=20173115 |doi=10.1182/blood-2009-09-239087 |url=}}</ref><ref name="pmid28641574">{{cite journal |vauthors=Medina SS, Siqueira LH, Colella MP, Yamaguti-Hayakawa GG, Duarte BKL, Dos Santos Vilela MM, Ozelo MC |title=Intermittent low platelet counts hampering diagnosis of X-linked thrombocytopenia in children: report of two unrelated cases and a novel mutation in the gene coding for the Wiskott-Aldrich syndrome protein |journal=BMC Pediatr |volume=17 |issue=1 |pages=151 |date=June 2017 |pmid=28641574 |pmc=5480256 |doi=10.1186/s12887-017-0897-6 |url=}}</ref><ref name="pmid24115682">{{cite journal |vauthors=Wada T, Itoh M, Maeba H, Toma T, Niida Y, Saikawa Y, Yachie A |title=Intermittent X-linked thrombocytopenia with a novel WAS gene mutation |journal=Pediatr Blood Cancer |volume=61 |issue=4 |pages=746–8 |date=April 2014 |pmid=24115682 |doi=10.1002/pbc.24787 |url=}}</ref>
+* There is a relationship between XLT and WAS as both are caused by mutations of the same gene.<ref name="pmid7795648">{{cite journal |vauthors=Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG |title=X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene |journal=Nat. Genet. |volume=9 |issue=4 |pages=414–7 |date=April 1995 |pmid=7795648 |doi=10.1038/ng0495-414 |url=}}</ref>
+* WAS gene is mutated in X linked [[thrombocytopenia]] .<ref name="pmid7795648">{{cite journal |vauthors=Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG |title=X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene |journal=Nat. Genet. |volume=9 |issue=4 |pages=414–7 |date=April 1995 |pmid=7795648 |doi=10.1038/ng0495-414 |url=}}</ref>
+*  X linked thrombocytopenia is inherited as a [[X linked-recessive|X- linked-recessive pattern.]]
+* X linked thrombocytopenia is characterized by:
+**Mild-to-moderate [[eczema]]
+**Mild infrequent infections
+**Small-sized platelets
-== X-linked thrombocytopenia (XLT) ==
+* Treatment for patients with XLT is still not determined.<ref name="pmid20173115">{{cite journal |vauthors=Albert MH, Bittner TC, Nonoyama S, Notarangelo LD, Burns S, Imai K, Espanol T, Fasth A, Pellier I, Strauss G, Morio T, Gathmann B, Noordzij JG, Fillat C, Hoenig M, Nathrath M, Meindl A, Pagel P, Wintergerst U, Fischer A, Thrasher AJ, Belohradsky BH, Ochs HD |title=X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options |journal=Blood |volume=115 |issue=16 |pages=3231–8 |date=April 2010 |pmid=20173115 |doi=10.1182/blood-2009-09-239087 |url=}}</ref>
-Presents with mild eczema and/or infections, it is suspected to be a variant of WAS.Patients with XLT shown to have mutations in the (WAS)Wiskott-Aldrich syndrome protein gene.
-X-linked thrombocytopenia (XLT) should be suspected in a male with:
+== WIP Deficiency ==
-* Congenital thrombocytopenia (5,000-50,000 platelets/mm3).
+* WIPF1 gene which is located on chromosome 2q31.1
-* Small platelet size (platelet volume <7.5 fL).
+* Mutation of WIPF1 gene leads to WIP deficiency.
-* Absence of other clinical findings of Wiskott-Aldrich syndrome.
-* Family history of one or more maternally related males with a WAS-related phenotype or disorder.
-* Decreased or absent WASP by flow cytometry or western blotting..
-* Some affected individuals have near-normal amounts of WAS.
-== WIP DEFICIENCY ==
+* WASP is totally complexed with the WASP-interacting protein (WIP).<ref name="pmid3260865">{{cite journal |vauthors=Caputo O, Grosa G, Balliano G, Rocco F, Biglino G |title=In vitro metabolism of 2-(5-ethylpyridin-2-yl)benzimidazole |journal=Eur J Drug Metab Pharmacokinet |volume=13 |issue=1 |pages=47–51 |date=1988 |pmid=3260865 |doi=10.1007/BF03189928 |url=}}</ref>
-NEED TO COMPLETE THIS (WIP)WISKOTT-ALDRICH-INTERACTING PROTEIN; gene :WIPF1 is located on  2q31.1  . lymphocytes, WASP is almost totally complexed with the WASP-interacting protein (WIP). A major function of WIP is to stabilize WASP and prevent its degradation. WASP protein levels, but not mRNA levels, are severely reduced in T cells <ref name="pmid1783416">{{cite journal |vauthors=Pawłowski R |title=Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population |journal=Hum. Hered. |volume=41 |issue=4 |pages=279–80 |date=1991 |pmid=1783416 |doi=10.1159/000154013 |url=}}</ref>
+* Deficiency of WIP leads to [[autosomal recessive]] form of [[Wiskott Aldrich syndrome]].
+* A main function of WIP is to stabilize WASP and prevents its degradation.
+* WASP [[protein]] levels are greatly reduced in [[T lymphocytes]].<ref name="pmid1783416">{{cite journal |vauthors=Pawłowski R |title=Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population |journal=Hum. Hered. |volume=41 |issue=4 |pages=279–80 |date=1991 |pmid=1783416 |doi=10.1159/000154013 |url=}}</ref>
+* The presentation is similar to [[Wiskott-Aldrich syndrome]] which includes followings:
+**[[Recurrent infections]]
+**[[Eczema]]
+**[[Thrombocytopenia]]
+* Immunologic analysis shows decreased numbers of [[B cells]] and [[T cells]], especialy [[CD8 + T cells|CD8+ T cells]].
+* [[Hematopoietic stem cell transplantation]] is the treatment of choice.<ref name="pmid27742395">{{cite journal |vauthors=Al-Mousa H, Hawwari A, Al-Ghonaium A, Al-Saud B, Al-Dhekri H, Al-Muhsen S, Elshorbagi S, Dasouki M, El-Baik L, Alseraihy A, Ayas M, Arnaout R |title=Hematopoietic stem cell transplantation corrects WIP deficiency |journal=J. Allergy Clin. Immunol. |volume=139 |issue=3 |pages=1039–1040.e4 |date=March 2017 |pmid=27742395 |doi=10.1016/j.jaci.2016.08.036 |url=}}</ref>
-==ARPC1B DEFICIENCY==
+==ARPC1B Deficiency==
-* ARPC1B gene (ACTIN-RELATED PROTEIN 2/3 COMPLEX, SUBUNIT 1B) is located on 7q22.1 and its deficieny leads to PLTEID(Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease)
+*ARPC1B is inherited as an [[autosomal recessive]] disorder.
-* The ARP2/3 protein complex is involved in the control of actin polymerization in cells. The human complex consists of 7 subunits, including the actin-related proteins ARP2 and ARP3 .<ref name="pmid11533442">{{cite journal |vauthors=Volkmann N, Amann KJ, Stoilova-McPhie S, Egile C, Winter DC, Hazelwood L, Heuser JE, Li R, Pollard TD, Hanein D |title=Structure of Arp2/3 complex in its activated state and in actin filament branch junctions |journal=Science |volume=293 |issue=5539 |pages=2456–9 |date=September 2001 |pmid=11533442 |doi=10.1126/science.1063025 |url=}}</ref>
+*[[ARPC1B]] also known as actin-related protein 2/3 complex, subunit 1B which is located on 7q22.1.
-* PLTEID is an autosomal recessive immune-mediated inflammatory disease with highly variable manifestations. More severely affected individuals have recurrent infections, vasculitis, and thrombocytopenia, whereas other patients have mild vasculitis and normal numbers of small platelets without severe infections.
+*The human complex consists of 7 subunits, including the actin-related proteins ARP2 and ARP3.
-* Laboratory studies show platelets with abnormal shape, decreased dense granules, and impaired spreading ability, as well as immune dysregulation with increased eosinophils, B cells, IgA and IgE, and autoantibodies <ref name="pmid28368018">{{cite journal |vauthors=Kahr WH, Pluthero FG, Elkadri A, Warner N, Drobac M, Chen CH, Lo RW, Li L, Li R, Li Q, Thoeni C, Pan J, Leung G, Lara-Corrales I, Murchie R, Cutz E, Laxer RM, Upton J, Roifman CM, Yeung RS, Brumell JH, Muise AM |title=Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease |journal=Nat Commun |volume=8 |issue= |pages=14816 |date=April 2017 |pmid=28368018 |pmc=5382316 |doi=10.1038/ncomms14816 |url=}}</ref>
+* [[ARPC1B]] complex is involved in the control of [[actin]] [[polymerization]] in cells.<ref name="pmid11533442">{{cite journal |vauthors=Volkmann N, Amann KJ, Stoilova-McPhie S, Egile C, Winter DC, Hazelwood L, Heuser JE, Li R, Pollard TD, Hanein D |title=Structure of Arp2/3 complex in its activated state and in actin filament branch junctions |journal=Science |volume=293 |issue=5539 |pages=2456–9 |date=September 2001 |pmid=11533442 |doi=10.1126/science.1063025 |url=}}</ref>
+*Deficiency of [[ARPC1B]] complex leads to [[platelet abnormalities with eosinophilia and immune-mediated inflammatory disease]].<ref name="KahrPluthero2017">{{cite journal|last1=Kahr|first1=Walter H. A.|last2=Pluthero|first2=Fred G.|last3=Elkadri|first3=Abdul|last4=Warner|first4=Neil|last5=Drobac|first5=Marko|last6=Chen|first6=Chang Hua|last7=Lo|first7=Richard W.|last8=Li|first8=Ling|last9=Li|first9=Ren|last10=Li|first10=Qi|last11=Thoeni|first11=Cornelia|last12=Pan|first12=Jie|last13=Leung|first13=Gabriella|last14=Lara-Corrales|first14=Irene|last15=Murchie|first15=Ryan|last16=Cutz|first16=Ernest|last17=Laxer|first17=Ronald M.|last18=Upton|first18=Julia|last19=Roifman|first19=Chaim M.|last20=Yeung|first20=Rae S. M.|last21=Brumell|first21=John H|last22=Muise|first22=Aleixo M|title=Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease|journal=Nature Communications|volume=8|year=2017|pages=14816|issn=2041-1723|doi=10.1038/ncomms14816}}</ref>
+*Severe manisfestations of ARPC1B deficiency include followings: <ref name="KuijpersTool2017">{{cite journal|last1=Kuijpers|first1=Taco W.|last2=Tool|first2=Anton T.J.|last3=van der Bijl|first3=Ivo|last4=de Boer|first4=Martin|last5=van Houdt|first5=Michel|last6=de Cuyper|first6=Iris M.|last7=Roos|first7=Dirk|last8=van Alphen|first8=Floris|last9=van Leeuwen|first9=Karin|last10=Cambridge|first10=Emma L.|last11=Arends|first11=Mark J.|last12=Dougan|first12=Gordon|last13=Clare|first13=Simon|last14=Ramirez-Solis|first14=Ramiro|last15=Pals|first15=Steven T.|last16=Adams|first16=David J.|last17=Meijer|first17=Alexander B.|last18=van den Berg|first18=Timo K.|title=Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency|journal=Journal of Allergy and Clinical Immunology|volume=140|issue=1|year=2017|pages=273–277.e10|issn=00916749|doi=10.1016/j.jaci.2016.09.061}}</ref>
+**[[Recurrent infections]]
+**[[Vasculitis]]
+**[[Thrombocytopenia]]
+*Less severe manisfestations include mild [[vasculitis]] and normal numbers of small [[platelets]] without severe infections.
+*Laboratory studies show [[platelets]] with [[abnormal shape|an abnormal shape]] and decreased [[dense]] [[granules]].
+*Levels of [[eosinophils]], B-[[B-cells|lymphocytes]], [[IgA]] and [[IgE]] are increased due to immune dysregulations.<ref name="pmid28368018">{{cite journal |vauthors=Kahr WH, Pluthero FG, Elkadri A, Warner N, Drobac M, Chen CH, Lo RW, Li L, Li R, Li Q, Thoeni C, Pan J, Leung G, Lara-Corrales I, Murchie R, Cutz E, Laxer RM, Upton J, Roifman CM, Yeung RS, Brumell JH, Muise AM |title=Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease |journal=Nat Commun |volume=8 |issue= |pages=14816 |date=April 2017 |pmid=28368018 |pmc=5382316 |doi=10.1038/ncomms14816 |url=}}</ref>
-==ATAXIA-TELANGIECTASIA==
+==Ataxia-telangietectasia==
-* Ataxia-telangiectasia (AT) is an autosomal recessive characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency
+* Ataxia-telangiectasia (AT) is an [[autosomal recessive]] disorder caused by defective  ATM gene.
-* The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control with defects in both cellular and humoral immunity <ref name="pmid9143686">{{cite journal |vauthors=Lavin MF, Shiloh Y |title=The genetic defect in ataxia-telangiectasia |journal=Annu. Rev. Immunol. |volume=15 |issue= |pages=177–202 |date=1997 |pmid=9143686 |doi=10.1146/annurev.immunol.15.1.177 |url=}}</ref>.
+* The ATM gene is located on chromosome 11q22.3.
-* ATM gene is located on 11q22.3.
+* ATM gene is involved in cell responses to [[DNA damage]] and cell cycle control.<ref name="pmid9143686">{{cite journal |vauthors=Lavin MF, Shiloh Y |title=The genetic defect in ataxia-telangiectasia |journal=Annu. Rev. Immunol. |volume=15 |issue= |pages=177–202 |date=1997 |pmid=9143686 |doi=10.1146/annurev.immunol.15.1.177 |url=}}</ref>
-* Diagnosis is usually achieved by  physical examination and identification of both ataxia and oculo-cutaneous telangiectasia, this is then followed by laboratory tests for low levels of IgA, IgG2, IgG4, and IgE.
+*Common manifestations of AT include followings:<ref name="pmid3200306">{{cite journal |vauthors=Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K |title=Localization of an ataxia-telangiectasia gene to chromosome 11q22-23 |journal=Nature |volume=336 |issue=6199 |pages=577–80 |date=December 1988 |pmid=3200306 |doi=10.1038/336577a0 |url=}}</ref><ref name="pmid10482258">{{cite journal |vauthors=Lewis RF, Lederman HM, Crawford TO |title=Ocular motor abnormalities in ataxia telangiectasia |journal=Ann. Neurol. |volume=46 |issue=3 |pages=287–95 |date=September 1999 |pmid=10482258 |doi= |url=}}</ref><ref name="pmid20583220">{{cite journal |vauthors=McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, Brody AS, Langston C, Fan LL, Lefton-Greif MA, Crawford TO, Troche M, Sandlund JT, Auwaerter PG, Easley B, Loughlin GM, Carroll JL, Lederman HM |title=Evaluation and management of pulmonary disease in ataxia-telangiectasia |journal=Pediatr. Pulmonol. |volume=45 |issue=9 |pages=847–59 |date=September 2010 |pmid=20583220 |pmc=4151879 |doi=10.1002/ppul.21277 |url=}}</ref><ref name="pmid23360865">{{cite journal |vauthors=Greenberger S, Berkun Y, Ben-Zeev B, Levi YB, Barziliai A, Nissenkorn A |title=Dermatologic manifestations of ataxia-telangiectasia syndrome |journal=J. Am. Acad. Dermatol. |volume=68 |issue=6 |pages=932–6 |date=June 2013 |pmid=23360865 |doi=10.1016/j.jaad.2012.12.950 |url=}}</ref>
-* They may also have a low lymphocyte count and other immunological abnormalities.
+**Neurologic abnormalities
-* This can then be followed by cytogenetic and molecular testing to confirm the diagnosis.
+***Progressive [[Cerebellar ataxias|cerebellar ataxia]]
-* MRI and CT scans may show signs of cerebellar atrophy.
+***Abnormal eye movements
+***Oculomotor apraxia
+***Mild to moderate [[cognitive impairment]]
+***[[Choreoathetosis]]
+**Dermatologic manifestations
+***[[Telangiectasias]] on exposed areas including pinnae, nose, face, and neck
+***Hypopigmented macules
+***Melanocytic nevi
+***Facial papulosquamous rash
+**[[Oculocutaneous]] [[Telangiectasia]]
+**Pulmonary disease
+***Recurrent sinopulmonary infections
+***[[Bronchiectasis]]
+***[[Interstitial lung disease]]
+***[[Pulmonary fibrosis]]
+**Neuromuscular abnormalities
+***[[Dysphagia]]
+***[[Aspiration]]
+***Respiratory muscle weakness
+*Diagnostic criteria for ataxia-telangiectasia includes followings:<ref name="pmid6163129">{{cite journal |vauthors=Wu JT, Book L, Sudar K |title=Serum alpha fetoprotein (AFP) levels in normal infants |journal=Pediatr. Res. |volume=15 |issue=1 |pages=50–2 |date=January 1981 |pmid=6163129 |doi= |url=}}</ref><ref name="pmid15486025">{{cite journal |vauthors=Butch AW, Chun HH, Nahas SA, Gatti RA |title=Immunoassay to measure ataxia-telangiectasia mutated protein in cellular lysates |journal=Clin. Chem. |volume=50 |issue=12 |pages=2302–8 |date=December 2004 |pmid=15486025 |doi=10.1373/clinchem.2004.039461 |url=}}</ref><ref name="pmid10600329">{{cite journal |vauthors=Conley ME, Notarangelo LD, Etzioni A |title=Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) |journal=Clin. Immunol. |volume=93 |issue=3 |pages=190–7 |date=December 1999 |pmid=10600329 |doi=10.1006/clim.1999.4799 |url=}}</ref>
+**Definitive diagnosis
+***Increased radiation-induced chromosomal breakage in cultured cells
+***Progressive cerebellar ataxia and who has disabling mutations on both alleles of ATM
+**Probable diagnosis
+***Ocular or facial [[Telangiectasias|telangiectasia]]
+***[[Serum IgA]] at least 2 SD below normal for age
+***[[Alpha fetoprotein]] at least 2 SD above normal for age
+***Increased [[radiation]]-induced [[chromosomal]] [[breakage]] in cultured [[cells]]
+* Diagnosis can also be made by rapid [[immunoblotting]] assay for [[ATM protein]] because its levels are greatly reduced.<ref name="pmid15486025">{{cite journal |vauthors=Butch AW, Chun HH, Nahas SA, Gatti RA |title=Immunoassay to measure ataxia-telangiectasia mutated protein in cellular lysates |journal=Clin. Chem. |volume=50 |issue=12 |pages=2302–8 |date=December 2004 |pmid=15486025 |doi=10.1373/clinchem.2004.039461 |url=}}</ref>
+* It leads to increased risk of development of [[lymphoid malignancies]] and [[immunodeficiency]].
+*[[Cerebellar]] [[atrophy]] will be seen on MRI or CT scan.
 ==Nijmegen breakage Syndrome==
-* Nijmegen breakage syndrome (NBS) is caused by mutation in the NBS1 gene on chromosome 8q21 which is inherited as an Autosomal Recessive disorder.
+*It is also known as Ataxia-telangiectasia variant-1.
-* It is characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer.
+* Nijmegen breakage syndrome (NBS) is caused by mutation in the [[NBS1]] [[gene]] which is located on [[chromosome]] 8q21.
-* It is phenotypically indistinguishable from Berlin breakage syndrome.Both are autosomal recessive chromosomal instability syndromes.
+* It is inherited as an [[autosomal]] [[recessive]] disorder.
-* Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome.
+*Common manifestations include followings:<ref name="pmid22373003">{{cite journal |vauthors=Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M |title=Nijmegen breakage syndrome (NBS) |journal=Orphanet J Rare Dis |volume=7 |issue= |pages=13 |date=February 2012 |pmid=22373003 |pmc=3314554 |doi=10.1186/1750-1172-7-13 |url=}}</ref><ref name="pmid22373003">{{cite journal |vauthors=Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M |title=Nijmegen breakage syndrome (NBS) |journal=Orphanet J Rare Dis |volume=7 |issue= |pages=13 |date=February 2012 |pmid=22373003 |pmc=3314554 |doi=10.1186/1750-1172-7-13 |url=}}</ref><ref name="pmid19105185">{{cite journal |vauthors=Warcoin M, Lespinasse J, Despouy G, Dubois d'Enghien C, Laugé A, Portnoï MF, Christin-Maitre S, Stoppa-Lyonnet D, Stern MH |title=Fertility defects revealing germline biallelic nonsense NBN mutations |journal=Hum. Mutat. |volume=30 |issue=3 |pages=424–30 |date=March 2009 |pmid=19105185 |doi=10.1002/humu.20904 |url=}}</ref><ref name="pmid20444919">{{cite journal |vauthors=Chrzanowska KH, Szarras-Czapnik M, Gajdulewicz M, Kalina MA, Gajtko-Metera M, Walewska-Wolf M, Szufladowicz-Wozniak J, Rysiewski H, Gregorek H, Cukrowska B, Syczewska M, Piekutowska-Abramczuk D, Janas R, Krajewska-Walasek M |title=High prevalence of primary ovarian insufficiency in girls and young women with Nijmegen breakage syndrome: evidence from a longitudinal study |journal=J. Clin. Endocrinol. Metab. |volume=95 |issue=7 |pages=3133–40 |date=July 2010 |pmid=20444919 |doi=10.1210/jc.2009-2628 |url=}}</ref>
+**[[Microcephaly]]
+**Dysmorphic facial features
+**Mild [[growth retardation]]
+**Mild-to-moderate [[intellectual disability]]
+**[[Café-au-lait spots]] and depigmented skin lesions
+**[[Ovarian dysgenesis]] and premature [[ovarian failure]] in females
+**Hypergonadotropic [[hypogonadism]] and [[infertility]] in males
+**Recurrent [[sinopulmonary]] [[infections]]
+* A strong predisposed to development of malignancies of lymphoid origin
+* The patients are also [[hypersensitive]] to double stand DNA breaking-inducing agents e.g ionizing [[radiations]].<ref name="pmid18724061">{{cite journal |vauthors=Antoccia A, Kobayashi J, Tauchi H, Matsuura S, Komatsu K |title=Nijmegen breakage syndrome and functions of the responsible protein, NBS1 |journal=Genome Dyn |volume=1 |issue= |pages=191–205 |date=2006 |pmid=18724061 |doi=10.1159/000092508 |url=}}</ref>
+* There is no specific treatment for NBS.
-==BLOOM SYNDROME==
+==Bloom Syndrome==
-* It is caused by the mutation in the BLM gene encoding DNA helicase RecQ protein-like-3 (RECQL3) on chromosome 15q26.
+* Bloom syndrome is also called as Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema.
-* also called Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema, is a rare autosomal recessive inherited disorder characterized by genomic instability and predisposition to the development all types of cancer.
+* Bloom syndrome is caused by the [[mutation]] in the BLM gene which is located on chromosome 15q26.
+* BLM gene encodes DNA helicase RecQ protein-like-3 (RECQL3).<ref name="pmid8875252">{{cite journal |vauthors=Ellis NA, German J |title=Molecular genetics of Bloom's syndrome |journal=Hum. Mol. Genet. |volume=5 Spec No |issue= |pages=1457–63 |date=1996 |pmid=8875252 |doi= |url=}}</ref><ref name="pmid8231788">{{cite journal |vauthors=German J |title=Bloom syndrome: a mendelian prototype of somatic mutational disease |journal=Medicine (Baltimore) |volume=72 |issue=6 |pages=393–406 |date=November 1993 |pmid=8231788 |doi= |url=}}</ref>
+* Bloom Syndrome is inherited as an [[autosomal recessive]] inherited disorder.
+* Most common manifestations of Bloom syndrome include followings:<ref name="pmid20973772">{{cite journal |vauthors=Karalis A, Tischkowitz M, Millington GW |title=Dermatological manifestations of inherited cancer syndromes in children |journal=Br. J. Dermatol. |volume=164 |issue=2 |pages=245–56 |date=February 2011 |pmid=20973772 |doi=10.1111/j.1365-2133.2010.10100.x |url=}}</ref><ref name="pmid8875252">{{cite journal |vauthors=Ellis NA, German J |title=Molecular genetics of Bloom's syndrome |journal=Hum. Mol. Genet. |volume=5 Spec No |issue= |pages=1457–63 |date=1996 |pmid=8875252 |doi= |url=}}</ref>
+**[[Growth]] deficiency of prenatal onset
+**[[Immunodeficiency]]
+**[[Café-au-lait spot|Café-au-lait]] spots or [[Hypopigmentation|hypopigmented]] skin lesions
+**Excessive [[photosensitivity]] with facial lupus-like skin lesions
+**[[Type 2 diabetes mellitus]]
+**[[Hypogonadism]]
+**Predisposition to the development of all types of [[cancers]]
+* Bloom syndrome is diagnosed by detecting mutations in BLM gene.<ref name="pmid18471088">{{cite journal |vauthors=Amor-Guéret M, Dubois-d'Enghien C, Laugé A, Onclercq-Delic R, Barakat A, Chadli E, Bousfiha AA, Benjelloun M, Flori E, Doray B, Laugel V, Lourenço MT, Gonçalves R, Sousa S, Couturier J, Stoppa-Lyonnet D |title=Three new BLM gene mutations associated with Bloom syndrome |journal=Genet. Test. |volume=12 |issue=2 |pages=257–61 |date=June 2008 |pmid=18471088 |doi=10.1089/gte.2007.0119 |url=}}</ref>
+*There is no specific treatment for bloom syndrome.
-* The most prominent features include growth deficiency of prenatal onset, mild immunodeficiency, excessive photosensitivity with facial lupus-like skin lesions, type 2 diabetes mellitus and hypogonadism.
+==PMS2 Deficiency==
+* PMS2 also known as Post-Meiotic Segregation 2.
-* Laboratory diagnosis of Bloom syndrome by detecting mutations in BLM .
+* PMS2 gene is located on [[chromosome]] 7p22.1
-==PMS2 deficiency==
-* PMS2 stands for POSTMEIOTIC SEGREGATION INCREASED, S. CEREVISIAE,
-* PMS2 gene is located on chromosome 7p22.1
-* PMS2 is a gene that encodes for DNA repair proteins involved in mismatch repair
-* Its Deficiency is inherited as Autosomal Recessive pattern which leads to Colorectal cancer, hereditary nonpolyposis akaMismatch repair cancer syndrome<ref name="pmid8072530">{{cite journal |vauthors=Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM |title=Mutations of two PMS homologues in hereditary nonpolyposis colon cancer |journal=Nature |volume=371 |issue=6492 |pages=75–80 |date=September 1994 |pmid=8072530 |doi=10.1038/371075a0 |url=}}</ref>
-== Immunodeficiency with centromeric instability and facial anomalies(ICF1, ICF2, ICF3, ICF4) ==
+* PMS2 gene  encodes for [[DNA]] [[repair]] [[proteins]] which are involved in DNA [[mismatch repair]].<ref name="pmid7172481">{{cite journal |vauthors=Michels VV, Stevens JC |title=Basal cell carcinoma in a patient with intestinal polyposis |journal=Clin. Genet. |volume=22 |issue=2 |pages=80–2 |date=August 1982 |pmid=7172481 |doi= |url=}}</ref>
-* ICF is caused by mutation in the ZBTB24 gene on chromosome 6q21; ICF3 is caused by mutation in the CDCA7 gene on chromosome 2q31; and ICF4 is caused by mutation in the HELLS gene on chromosome 10q23.
-* It is an autosomal recessive disease presenting with immunodeficiency, mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation.
+* PMS2 Deficiency is inherited as [[autosomal recessive]] pattern.<ref name="pmid24737826">{{cite journal |vauthors=Wimmer K, Kratz CP, Vasen HF, Caron O, Colas C, Entz-Werle N, Gerdes AM, Goldberg Y, Ilencikova D, Muleris M, Duval A, Lavoine N, Ruiz-Ponte C, Slavc I, Burkhardt B, Brugieres L |title=Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD) |journal=J. Med. Genet. |volume=51 |issue=6 |pages=355–65 |date=June 2014 |pmid=24737826 |doi=10.1136/jmedgenet-2014-102284 |url=}}</ref>
-* Serum levels of IgG, IgM, IgE, and/or IgA are low.
+* Deficiency of PMS2 increases the risk of [[colorectal cancer]] and [[Hereditary nonpolyposis colorectal cancer (patient information)|hereditary nonpolyposis]].<ref name="pmid8072530">{{cite journal |vauthors=Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM |title=Mutations of two PMS homologues in hereditary nonpolyposis colon cancer |journal=Nature |volume=371 |issue=6492 |pages=75–80 |date=September 1994 |pmid=8072530 |doi=10.1038/371075a0 |url=}}</ref>
-* Recurrent infections are the presenting symptom, usually in early childhood.
-* The differentials include Bloom syndrome, ataxia-telangiectasia, and Nijmegen breakage syndrome
-* Treatment almost always includes regular infusions of immunoglobulins, mostly intravenously
-* Recently, bone marrow transplantation has been tried.
-==MCM4 deficiency==
+== Immunodeficiency with Centromeric instability and Facial anomalies(ICF1, ICF2, ICF3, ICF4) ==
-* MCM stands for MINICHROMOSOME MAINTENANCE, S. CEREVISIAE, HOMOLOG OF 4
+* ICF2 is caused by [[Mutations|mutation]] in the ZBTB24 gene on chromosome 6q21.<ref name="pmid15580563">{{cite journal |vauthors=Jiang YL, Rigolet M, Bourc'his D, Nigon F, Bokesoy I, Fryns JP, Hultén M, Jonveaux P, Maraschio P, Mégarbané A, Moncla A, Viegas-Péquignot E |title=DNMT3B mutations and DNA methylation defect define two types of ICF syndrome |journal=Hum. Mutat. |volume=25 |issue=1 |pages=56–63 |date=January 2005 |pmid=15580563 |doi=10.1002/humu.20113 |url=}}</ref>
-* Deficiency caused by homozygous mutation in the MCM4 gene located on 8q11.21 <ref name="pmid3287227">{{cite journal |vauthors=Villa A, Sinchetto F, Lanfranconi M |title=[Pathology of the myocardium and coronary vessels in sudden cardiac death. A post-mortem study of 130 cases] |language=Italian |journal=Minerva Med. |volume=79 |issue=5 |pages=373–8 |date=May 1988 |pmid=3287227 |doi= |url=}}</ref>
+* ICF3 is caused by [[Mutations|mutation]] in the CDCA7 gene on chromosome 2q31.
-* Tt is a variant of familial glucocorticoid deficiency (FGD), an autosomal recessive form of adrenal failure
+* ICF4 is caused by [[mutation]] in the HELLS gene on chromosome 10q23.
-* MCM4 is one part of a MCM2-7 complex whic functions as the replicative helicase essential for normal DNA replication and genome stability in all eukaryotes
-* It characterized by adrenal insufficiency, short stature, and NK cell deficiency.
-* The NK cell deficiency accounts for the patients' recurrent viral illnesses
-* Patients have typical biochemical features of FGD, with isolated glucocorticoid deficiency, raised ACTH, and normal renin and aldosterone.
-* Affected individuals with adrenal insufficiency requiring corticosteroid replacement therapy
-==RNF168 deficiency==
+* It is an [[autosomal recessive]] disease.
-* IT STANDS FOR RING FINGER PROTEIN 168(RNF168)
+*Common manifestations of ICF include followings:<ref name="pmid3351904">{{cite journal |vauthors=Maraschio P, Zuffardi O, Dalla Fior T, Tiepolo L |title=Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome |journal=J. Med. Genet. |volume=25 |issue=3 |pages=173–80 |date=March 1988 |pmid=3351904 |pmc=1015482 |doi= |url=}}</ref><ref name="pmid8102570">{{cite journal |vauthors=Jeanpierre M, Turleau C, Aurias A, Prieur M, Ledeist F, Fischer A, Viegas-Pequignot E |title=An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome |journal=Hum. Mol. Genet. |volume=2 |issue=6 |pages=731–5 |date=June 1993 |pmid=8102570 |doi= |url=}}</ref>
-* Gene is located on chromosome 3q29
+**[[Immunodeficiency]]
-* It codes E3 ubiquitin ligase which is critical for Double strand DNA breaks repair.<ref name="pmid19203578">{{cite journal |vauthors=Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, Oldreive C, Wildenhain J, Tagliaferro A, Pelletier L, Taubenheim N, Durandy A, Byrd PJ, Stankovic T, Taylor AM, Durocher D |title=The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage |journal=Cell |volume=136 |issue=3 |pages=420–34 |date=February 2009 |pmid=19203578 |doi=10.1016/j.cell.2008.12.042 |url=}}</ref>
+**[[facial dysmorphism]]
-* Mutation of this gene leads to RIDDLE syndrome.
+***[[Ocular hypertelorism]]
-* This sydrome is inherited as an Autosomal Recessive pattern
+***[[Flat nasal bridge]]
-* RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties) syndrome is an immunodeficiency disorder that primarily manifests as an immunoglobulin deficiency,also present with nonimmunological characteristics including short stature and motor control problems
+***[[Epicanthal folds|Epicanthal fold]]
+***[[Low-set ears]]
+**[[Growth retardation]]
+**[[Failure to thrive]]
+**[[Psychomotor retardation]]
+* The presenting symptom is recurrent infections usually in early childhood.
+* At least two [[immunoglobulin]] classes are affected in each patient and [[agammaglobulinemia]] can occur.
+* [[T cell]] number and response to [[mitogen]] may be decreased.<ref name="pmid8076938">{{cite journal |vauthors=Smeets DF, Moog U, Weemaes CM, Vaes-Peeters G, Merkx GF, Niehof JP, Hamers G |title=ICF syndrome: a new case and review of the literature |journal=Hum. Genet. |volume=94 |issue=3 |pages=240–6 |date=September 1994 |pmid=8076938 |doi= |url=}}</ref><ref name="pmid2386052">{{cite journal |vauthors=Fasth A, Forestier E, Holmberg E, Holmgren G, Nordenson I, Söderström T, Wahlström J |title=Fragility of the centromeric region of chromosome 1 associated with combined immunodeficiency in siblings. A recessively inherited entity? |journal=Acta Paediatr Scand |volume=79 |issue=6-7 |pages=605–12 |date=1990 |pmid=2386052 |doi= |url=}}</ref><ref name="pmid3351904">{{cite journal |vauthors=Maraschio P, Zuffardi O, Dalla Fior T, Tiepolo L |title=Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome |journal=J. Med. Genet. |volume=25 |issue=3 |pages=173–80 |date=March 1988 |pmid=3351904 |pmc=1015482 |doi= |url=}}</ref>
+* The [[centromeric]] instability most frequently involves chromosomes 1 and 16, often 9, and rarely 2 and 10.
+* The differential diagnosis include [[Bloom syndrome]], ataxia-telangiectasia, and [[Nijmegen breakage syndrome]].
+* [[Immunoglobulin]] should be given in the early phase.<ref name="pmid17893117">{{cite journal |vauthors=Hagleitner MM, Lankester A, Maraschio P, Hultén M, Fryns JP, Schuetz C, Gimelli G, Davies EG, Gennery A, Belohradsky BH, de Groot R, Gerritsen EJ, Mattina T, Howard PJ, Fasth A, Reisli I, Furthner D, Slatter MA, Cant AJ, Cazzola G, van Dijken PJ, van Deuren M, de Greef JC, van der Maarel SM, Weemaes CM |title=Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) |journal=J. Med. Genet. |volume=45 |issue=2 |pages=93–9 |date=February 2008 |pmid=17893117 |doi=10.1136/jmg.2007.053397 |url=}}</ref>
+* Severe cases can be treated with [[allogeneic]] [[hematopoietic]] cell transplantation.<ref name="pmid17908720">{{cite journal |vauthors=Gennery AR, Slatter MA, Bredius RG, Hagleitner MM, Weemaes C, Cant AJ, Lankester AC |title=Hematopoietic stem cell transplantation corrects the immunologic abnormalities associated with immunodeficiency-centromeric instability-facial dysmorphism syndrome |journal=Pediatrics |volume=120 |issue=5 |pages=e1341–4 |date=November 2007 |pmid=17908720 |doi=10.1542/peds.2007-0640 |url=}}</ref>
+==MCM4 Deficiency==
+* MCM stands for [[minichromosome]] maintenance complex component 4. MCM4 is one part of a MCM2-7 complex which functions as the replicative [[helicase]] which is essential for normal [[DNA]] replication and [[genome]] stability.
+* MCM4 deficiency is caused by [[mutation]] in the MCM4 [[gene]] located on 8q11.21. <ref name="pmid3287227">{{cite journal |vauthors=Villa A, Sinchetto F, Lanfranconi M |title=[Pathology of the myocardium and coronary vessels in sudden cardiac death. A post-mortem study of 130 cases] |language=Italian |journal=Minerva Med. |volume=79 |issue=5 |pages=373–8 |date=May 1988 |pmid=3287227 |doi= |url=}}</ref>
+* MCM4 deficiency is characterized by:<ref name="pmid22354167">{{cite journal |vauthors=Gineau L, Cognet C, Kara N, Lach FP, Dunne J, Veturi U, Picard C, Trouillet C, Eidenschenk C, Aoufouchi S, Alcaïs A, Smith O, Geissmann F, Feighery C, Abel L, Smogorzewska A, Stillman B, Vivier E, Casanova JL, Jouanguy E |title=Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency |journal=J. Clin. Invest. |volume=122 |issue=3 |pages=821–32 |date=March 2012 |pmid=22354167 |pmc=3287233 |doi=10.1172/JCI61014 |url=}}</ref>
+**[[Short stature]]
+**[[Adrenal insufficiency]]
+**[[NK cell deficiency]] which leads to recurrent [[viral]] illnesses<ref name="pmid22499342">{{cite journal |vauthors=Casey JP, Nobbs M, McGettigan P, Lynch S, Ennis S |title=Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair |journal=J. Med. Genet. |volume=49 |issue=4 |pages=242–5 |date=April 2012 |pmid=22499342 |doi=10.1136/jmedgenet-2012-100803 |url=}}</ref><ref name="pmid16532402">{{cite journal |vauthors=Eidenschenk C, Dunne J, Jouanguy E, Fourlinnie C, Gineau L, Bacq D, McMahon C, Smith O, Casanova JL, Abel L, Feighery C |title=A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8 |journal=Am. J. Hum. Genet. |volume=78 |issue=4 |pages=721–7 |date=April 2006 |pmid=16532402 |pmc=1424699 |doi=10.1086/503269 |url=}}</ref>
+* MCM4 deficiency is a variant of familial [[glucocorticoid]] deficiency (FGD), an [[autosomal recessive]] form of adrenal failure.<ref name="pmid16532402" />
+* MCM4 deficiency shares biochemical features of familial [[glucocorticoid]] deficiency, with isolated [[glucocorticoid]] deficiency, increased [[ACTH]], and normal [[aldosterone]] and [[renin]] levels.
+* Individuals with [[adrenal insufficiency]] should be given [[corticosteroid]] replacement therapy.
+==RNF168 Deficiency==
+* RNF168 stands for Ring finger protein 168(RNF168).
+* RNF168 gene is located on chromosome 3q29.<ref name="pmid21394101">{{cite journal |vauthors=Devgan SS, Sanal O, Doil C, Nakamura K, Nahas SA, Pettijohn K, Bartek J, Lukas C, Lukas J, Gatti RA |title=Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia |journal=Cell Death Differ. |volume=18 |issue=9 |pages=1500–6 |date=September 2011 |pmid=21394101 |pmc=3178430 |doi=10.1038/cdd.2011.18 |url=}}</ref>
+* RNF168 gene encodes E3 ubiquitin ligase which is involved in repair of double strand [[DNA]] breaks.<ref name="pmid19203578">{{cite journal |vauthors=Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, Oldreive C, Wildenhain J, Tagliaferro A, Pelletier L, Taubenheim N, Durandy A, Byrd PJ, Stankovic T, Taylor AM, Durocher D |title=The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage |journal=Cell |volume=136 |issue=3 |pages=420–34 |date=February 2009 |pmid=19203578 |doi=10.1016/j.cell.2008.12.042 |url=}}</ref>
+* Mutation of RNF168 gene leads to RIDDLE syndrome which is inherited as an [[autosomal]] [[recessive]] pattern.<ref name="pmid17940005">{{cite journal |vauthors=Stewart GS, Stankovic T, Byrd PJ, Wechsler T, Miller ES, Huissoon A, Drayson MT, West SC, Elledge SJ, Taylor AM |title=RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=43 |pages=16910–5 |date=October 2007 |pmid=17940005 |pmc=2040433 |doi=10.1073/pnas.0708408104 |url=}}</ref>
+* RIDDLE syndrome is characterized by:<ref name="pmid17940005">{{cite journal |vauthors=Stewart GS, Stankovic T, Byrd PJ, Wechsler T, Miller ES, Huissoon A, Drayson MT, West SC, Elledge SJ, Taylor AM |title=RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=43 |pages=16910–5 |date=October 2007 |pmid=17940005 |pmc=2040433 |doi=10.1073/pnas.0708408104 |url=}}</ref>
+**[[Radio-sensitivity]]
+**[[Immunodeficiency]]
+**Dysmorphic features
+**[[Learning difficulties]]
+**[[Short stature]]
+**Motor control problems
+* It is pathologically similar to the [[Ataxia telangiectasia|ataxia-telangiectasia syndrome]].<ref name="pmid19203578">{{cite journal |vauthors=Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, Oldreive C, Wildenhain J, Tagliaferro A, Pelletier L, Taubenheim N, Durandy A, Byrd PJ, Stankovic T, Taylor AM, Durocher D |title=The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage |journal=Cell |volume=136 |issue=3 |pages=420–34 |date=February 2009 |pmid=19203578 |doi=10.1016/j.cell.2008.12.042 |url=}}</ref>
 ==POLE1 deficiency==
-* POLYMERASE, DNA, EPSILON-1; POLE1
+* POLE1 stands for DNA polymerase, epsilon subunit 1.
-* Gene location: 12q24.33
+* The POLE1 gene is located on chromosome 12q24.33.
-* gene function: POLE gene encodes the catalytic subunit of DNA polymerase epsilon
+* POLE1 gene encodes the catalytic subunit of DNA polymerase epsilon.
-* Inheritance pattern: AR
+* POLE1 deficiency is inherited as an [[autosomal recessive]] pattern.
-* Disease:Facial dysmorphism-immunodeficiency-livedo-short stature syndrome (FILS syndrome)<ref name="pmid3526359">{{cite journal |vauthors=Tamaro M, Dolzani L, Monti-Bragadin C, Sava G |title=Mutagenic activity of the dacarbazine analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt in bacterial cells |journal=Pharmacol Res Commun |volume=18 |issue=5 |pages=491–501 |date=May 1986 |pmid=3526359 |doi= |url=}}</ref>
+* Mutation in the POLE1 leads to FILS syndrome.
-* If the pole gene mutation is inherited as an autosomal dominant patter then it leads to COLORECTAL CANCER, SUSCEPTIBILITY TO, 12
+* The age of onset of FILS syndrome is less than 40 years.<ref name="pmid23263490">{{cite journal |vauthors=Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Guarino E, Guarino Almeida E, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJ, McVean G, Houlston RS, Tomlinson I |title=Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas |journal=Nat. Genet. |volume=45 |issue=2 |pages=136–44 |date=February 2013 |pmid=23263490 |pmc=3785128 |doi=10.1038/ng.2503 |url=}}</ref>
+* It is characterized by:
+**Facial [[dysmorphism]]
+**[[Immunodeficiencies]]
+**Livedo on the skin since birth
+**[[Short stature]]<ref name="pmid3526359">{{cite journal |vauthors=Tamaro M, Dolzani L, Monti-Bragadin C, Sava G |title=Mutagenic activity of the dacarbazine analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt in bacterial cells |journal=Pharmacol Res Commun |volume=18 |issue=5 |pages=491–501 |date=May 1986 |pmid=3526359 |doi= |url=}}</ref><ref name="pmid23230001">{{cite journal |vauthors=Pachlopnik Schmid J, Lemoine R, Nehme N, Cormier-Daire V, Revy P, Debeurme F, Debré M, Nitschke P, Bole-Feysot C, Legeai-Mallet L, Lim A, de Villartay JP, Picard C, Durandy A, Fischer A, de Saint Basile G |title=Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short [[stature]] ("FILS syndrome") |journal=J. Exp. Med. |volume=209 |issue=13 |pages=2323–30 |date=December 2012 |pmid=23230001 |pmc=3526359 |doi=10.1084/jem.20121303 |url=}}</ref>
+* If the mutation in [[POLE1 gene]] is inherited as an [[Dominant disease|autosomal dominant]] pattern, it leads to [[colorectal cancer]]-12 which is characterized by a high predisposition of [[colorectal]] [[adenomas]] and [[carcinomas]].
 ==POLE2 deficiency==
-POLYMERASE, DNA, EPSILON-2; POLE2
+* POLE2 stands for DNA polymerase epsilon subunit 2.<ref name="pmid9405441">{{cite journal |vauthors=Li Y, Asahara H, Patel VS, Zhou S, Linn S |title=Purification, cDNA cloning, and gene mapping of the small subunit of human DNA polymerase epsilon |journal=J. Biol. Chem. |volume=272 |issue=51 |pages=32337–44 |date=December 1997 |pmid=9405441 |doi= |url=}}</ref>
-q21.3
+* POLE2 gene is located on choromosome 14q21.
-involved in both DNA replication and DNA repair,
+* POLE2 is involved in both [[DNA]] [[replication]] and [[DNA]] repair.
-AR
+* POLE2 deficiency is inherited as an [[autosomal recessive]] pattern.
-Mutation in the POLE2 Gene Causing Combined Immunodeficiency
+* POLE2 deficiency is characterized by the followings:
+**Combined [[immunodeficiencies]]
-==NSMCE3 deficiency==
+**[[Facial dysmorphism]]
-* NONSTRUCTURAL MAINTENANCE OF CHROMOSOMES ELEMENT 3 HOMOLOG; NSMCE3
+**[[Autoimmunity]]<ref name="pmid4747780">{{cite journal |vauthors=Miller MJ |title=Industrialization, ecology and health in the tropics |journal=Can J Public Health |volume=64 |issue= |pages=Suppl: 11–6 |date=October 1973 |pmid=4747780 |doi= |url=}}</ref>
-* The NSMCE3 gene encodes a component of the SMC5/SMC6complex, which is essential for responses to DNA damage and chromosome segregation during cell division
-* 15q13.1
-* AR
-* Lung disease, immunodeficiency, and chromosome breakage syndrome
-* Defective T and B cell function and acute respiratory distress syndrome in early childhood.
-<ref name="pmid4966312">{{cite journal |vauthors=Rickenbacher J |title=The importance of the regulation for the normal and abnormal development. Experimental investigations on the limb buds of chick embryos |journal=Biol Neonat |volume=12 |issue=1 |pages=65–87 |date=1968 |pmid=4966312 |doi= |url=}}</ref>
-==ERCC6L2(Hebo deficiency)==
+==NSMCE3 Deficiency==
-* HEBO stands for HELICASE MUTATED IN BONE MARROW FAILURE
+* NSMCE3 stands for non structural maintenance of chromosomes element 3.
-* ERCC6L2 gene is located on 9q22.32 ERCC6L2 belongs to a family of helicases
+* NSMCE3 [[gene]] is located on chromosome 15q13.1.
-* the gene is involved inchromatin unwinding, transcription regulation, and DNA recombination, translocation, and repair
+* NSMCE3 gene encodes a component of the SMC5/SMC6complex.
-* Mutation of this gene leads to Bone marrow failure syndrome 2
+* SMC5/SMC6 complex is important for responses to [[DNA]] damage and [[chromosome]] [[segregation]] during [[cell]] [[division]].<ref name="pmid27427983">{{cite journal |vauthors=van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, Harakalova M, Chinn IK, Alt A, Vondrova L, Hochstenbach R, van Montfrans JM, Terheggen-Lagro SW, van Lieshout S, van Roosmalen MJ, Renkens I, Duran K, Nijman IJ, Kloosterman WP, Hennekam E, Orange JS, van Hasselt PM, Wheeler DA, Palecek JJ, Lehmann AR, Oliver AW, Pearl LH, Plon SE, Murray JM, van Haaften G |title=Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease |journal=J. Clin. Invest. |volume=126 |issue=8 |pages=2881–92 |date=August 2016 |pmid=27427983 |pmc=4966312 |doi=10.1172/JCI82890 |url=}}</ref>
-* It is inherited as an autosomal pattern
+* LICS syndrome is inherited as an [[autosomal recessive]] pattern.
-* Characterized by trilineage bone marrow failure, learning disabilities, and microcephaly
+* Mutation in the NSMCE3 gene leads to LICS syndrome.
-<ref name="pmid24507776">{{cite journal |vauthors=Tummala H, Kirwan M, Walne AJ, Hossain U, Jackson N, Pondarre C, Plagnol V, Vulliamy T, Dokal I |title=ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function |journal=Am. J. Hum. Genet. |volume=94 |issue=2 |pages=246–56 |date=February 2014 |pmid=24507776 |pmc=3928664 |doi=10.1016/j.ajhg.2014.01.007 |url=}}</ref>
+* LICS stands for:
+**[[Lung disease]]
+**[[Immunodeficiencies]]
+**[[Chromosome]] breakage syndrome
+* Other features include:
+** Defective [[T cells]] and [[B cell]]
+** [[Acute respiratory distress syndrome]] in early childhood<ref name="pmid4966312">{{cite journal |vauthors=Rickenbacher J |title=The importance of the regulation for the normal and abnormal development. Experimental investigations on the limb buds of chick embryos |journal=Biol Neonat |volume=12 |issue=1 |pages=65–87 |date=1968 |pmid=4966312 |doi= |url=}}</ref>
-==Ligase 1 deficiency==
+==ERCC6L2 (Hebo deficiency)==
+* ERCC6L2 gene is located on chromosome 9q22.32.
+* ERCC6L2 gene belongs to a family of helicases.
+* ERCC6L2 gene is involved in chromatin unwinding, transcription regulation, DNA recombination, and repair.<ref name="pmid24507776">{{cite journal |vauthors=Tummala H, Kirwan M, Walne AJ, Hossain U, Jackson N, Pondarre C, Plagnol V, Vulliamy T, Dokal I |title=ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function |journal=Am. J. Hum. Genet. |volume=94 |issue=2 |pages=246–56 |date=February 2014 |pmid=24507776 |pmc=3928664 |doi=10.1016/j.ajhg.2014.01.007 |url=}}</ref>
+* Mutation of ERCC6L2 gene leads to bone marrow failure syndrome 2 which is inherited as an [[autosomal recessive]] pattern.<ref name="pmid24507776">{{cite journal |vauthors=Tummala H, Kirwan M, Walne AJ, Hossain U, Jackson N, Pondarre C, Plagnol V, Vulliamy T, Dokal I |title=ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function |journal=Am. J. Hum. Genet. |volume=94 |issue=2 |pages=246–56 |date=February 2014 |pmid=24507776 |pmc=3928664 |doi=10.1016/j.ajhg.2014.01.007 |url=}}</ref>
+* Bone marrow failure syndrome 2 is characterized by the followings:
+**Trilineage [[bone marrow failure]]
+**[[Learning disabilities]]
+**[[Microcephaly]]<ref name="pmid24507776">{{cite journal |vauthors=Tummala H, Kirwan M, Walne AJ, Hossain U, Jackson N, Pondarre C, Plagnol V, Vulliamy T, Dokal I |title=ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function |journal=Am. J. Hum. Genet. |volume=94 |issue=2 |pages=246–56 |date=February 2014 |pmid=24507776 |pmc=3928664 |doi=10.1016/j.ajhg.2014.01.007 |url=}}</ref>
-LIGASE I, DNA, ATP-DEPENDENT; LIG1
+==Ligase 1 Deficiency==
-q13.33
+* LIG1 gene is located on chromosome 19q13.33.
-LIG1 functions at the replication fork to join Okazaki fragments during replication of lagging strand DNA
+* LIG1 gene encodes DNA ligase.
-mutation of this gene leads to  RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE (formerly called as DNA LIGASE I DEFICIENCY
+* DNA ligase function at the replication fork is to join okazaki fragments during replication of lagging strand DNA.<ref name="pmid12124343">{{cite journal |vauthors=Harrison C, Ketchen AM, Redhead NJ, O'Sullivan MJ, Melton DW |title=Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene |journal=Cancer Res. |volume=62 |issue=14 |pages=4065–74 |date=July 2002 |pmid=12124343 |doi= |url=}}</ref>
-Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents.
+* Mutation of LIIG1 gene leads to reclassified-variant of unknown significance formerly called as DNA ligase 1 deficiency.
-<ref name="pmid1581963">{{cite journal |vauthors=Barnes DE, Tomkinson AE, Lehmann AR, Webster AD, Lindahl T |title=Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents |journal=Cell |volume=69 |issue=3 |pages=495–503 |date=May 1992 |pmid=1581963 |doi= |url=}}</ref>
+* Ligase 1 deficiency is characterized by:
+** [[Immunodeficiency]]
+** [[Cellular]] [[hypersensitivity]] to [[DNA]]-damaging agents<ref name="pmid1581963">{{cite journal |vauthors=Barnes DE, Tomkinson AE, Lehmann AR, Webster AD, Lindahl T |title=Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents |journal=Cell |volume=69 |issue=3 |pages=495–503 |date=May 1992 |pmid=1581963 |doi= |url=}}</ref>
 ==GINS1 deficiency==
-* gene :GINS1
+* GINS1 gene is located on [[chromosome]] 20p11.2.
-* location :  20p11.21
+* GINS1 gene encodes GINS complex.
-* protein: GINS complex
+* GINS1 deficiency is inherited as an [[autosomal recessive]] pattern.
-* Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency
+* GINS1 deficiency is characterized by followings:
-<ref name="pmid28414293">{{cite journal |vauthors=Cottineau J, Kottemann MC, Lach FP, Kang YH, Vély F, Deenick EK, Lazarov T, Gineau L, Wang Y, Farina A, Chansel M, Lorenzo L, Piperoglou C, Ma CS, Nitschke P, Belkadi A, Itan Y, Boisson B, Jabot-Hanin F, Picard C, Bustamante J, Eidenschenk C, Boucherit S, Aladjidi N, Lacombe D, Barat P, Qasim W, Hurst JA, Pollard AJ, Uhlig HH, Fieschi C, Michon J, Bermudez VP, Abel L, de Villartay JP, Geissmann F, Tangye SG, Hurwitz J, Vivier E, Casanova JL, Smogorzewska A, Jouanguy E |title=Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency |journal=J. Clin. Invest. |volume=127 |issue=5 |pages=1991–2006 |date=May 2017 |pmid=28414293 |pmc=5409070 |doi=10.1172/JCI90727 |url=}}</ref>
+**[[Natural killer T cell|Natural killer]] cell deficiency
+**Chronic neutropenia
-===Immuno-osseous dysplasias===
+**[[Intrauterine growth retardation]]
+**Mild facial dysmorphism
+**[[Eczematous Scaling|Eczematous]] skin
+**Recurrent [[infections]]<ref name="pmid28414293">{{cite journal |vauthors=Cottineau J, Kottemann MC, Lach FP, Kang YH, Vély F, Deenick EK, Lazarov T, Gineau L, Wang Y, Farina A, Chansel M, Lorenzo L, Piperoglou C, Ma CS, Nitschke P, Belkadi A, Itan Y, Boisson B, Jabot-Hanin F, Picard C, Bustamante J, Eidenschenk C, Boucherit S, Aladjidi N, Lacombe D, Barat P, Qasim W, Hurst JA, Pollard AJ, Uhlig HH, Fieschi C, Michon J, Bermudez VP, Abel L, de Villartay JP, Geissmann F, Tangye SG, Hurwitz J, Vivier E, Casanova JL, Smogorzewska A, Jouanguy E |title=Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency |journal=J. Clin. Invest. |volume=127 |issue=5 |pages=1991–2006 |date=May 2017 |pmid=28414293 |pmc=5409070 |doi=10.1172/JCI90727 |url=}}</ref>
-==Cartilage Hair Hypoplasia  !==
+==Cartilage hair hypoplasia==
-* Also known as METAPHYSEAL CHONDRODYSPLASIA
+* Cartilage hair hypoplasia is also known as metaphyseal chondroplasia.
-* It is caused by homozygous or compound heterozygous mutation in the RMRP gene on chromosome 9p13.
+* Cartilage hair hypoplasia  is caused by mutation in the RMRP gene.
-* The gene endoribonuclease RNase MRP consists of an RNA molecule bound to several proteins
+* RMRP gene is located on chromosome 9p13.
-* It has two functions :cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA.<ref name="pmid11207361">{{cite journal |vauthors=Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, Mäkitie O, Kaitila I, de la Chapelle A |title=Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia |journal=Cell |volume=104 |issue=2 |pages=195–203 |date=January 2001 |pmid=11207361 |doi= |url=}}</ref>
+* RMRP gene encodes mitochondrial RNA-processing endoribonuclease which is involved in cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA.<ref name="pmid11207361">{{cite journal |vauthors=Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, Mäkitie O, Kaitila I, de la Chapelle A |title=Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia |journal=Cell |volume=104 |issue=2 |pages=195–203 |date=January 2001 |pmid=11207361 |doi= |url=}}</ref><ref name="pmid11207361">{{cite journal |vauthors=Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, Mäkitie O, Kaitila I, de la Chapelle A |title=Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia |journal=Cell |volume=104 |issue=2 |pages=195–203 |date=January 2001 |pmid=11207361 |doi= |url=}}</ref>
-* Muatation is nherited as an Autosomal Recessive pattern characterized by short-limbed short stature and fine, sparse hair
+* Cartilage hair hypoplasia is inherited as an [[autosomal recessive]] pattern.
-* It also includes ligamentous laxity, defective immunity, hypoplastic anemia, and neuronal dysplasia of the intestine.
+* Cartilage hair hypoplasia is characterized by the followings:
-* CHH is diagnosed clinically by observing fine and often sparse hair in an individual with short stature with disproportionally short limbs.
+**Short limbs
-* Radiographic findings are helpful in the work-up of an individual with suspected skeletal dysplasia.
+**[[Short stature]]
-* The metaphyseal ends are abnormal in CHH and appear as scalloped, irregular surfaces that may contain cystic areas on routine radiographs<ref name="pmid1437368">{{cite journal |vauthors=Mäkitie O, Marttinen E, Kaitila I |title=Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients |journal=Pediatr Radiol |volume=22 |issue=6 |pages=434–9 |date=1992 |pmid=1437368 |doi= |url=}}</ref>
+**Fine and sparse hair
-* Genetic analysis of the RMRP gene confirms the diagnosis
+**[[Ligamentous]] laxity
+**Defective immunity
+**[[Hypoplastic]] [[anemia]]
+**Neuronal [[dysplasia]] of the intestine<ref name="pmid14284412">{{cite journal |vauthors=MCKUSICK VA, ELDRIDGE R, HOSTETLER JA, RUANGWIT U, EGELAND JA |title=DWARFISM IN THE AMISH. II. CARTILAGE-HAIR HYPOPLASIA |journal=Bull Johns Hopkins Hosp |volume=116 |issue= |pages=285–326 |date=May 1965 |pmid=14284412 |doi= |url=}}</ref><ref name="pmid11207361">{{cite journal |vauthors=Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, Mäkitie O, Kaitila I, de la Chapelle A |title=Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia |journal=Cell |volume=104 |issue=2 |pages=195–203 |date=January 2001 |pmid=11207361 |doi= |url=}}</ref>
+* Clinical diagnosis is made by observing fine and sometimes sparse hair in an individual with short stature and disproportionally short limbs.<ref name="pmid19150606">{{cite journal |vauthors=Rider NL, Morton DH, Puffenberger E, Hendrickson CL, Robinson DL, Strauss KA |title=Immunologic and clinical features of 25 Amish patients with RMRP 70 A-->G cartilage hair hypoplasia |journal=Clin. Immunol. |volume=131 |issue=1 |pages=119–28 |date=April 2009 |pmid=19150606 |doi=10.1016/j.clim.2008.11.001 |url=}}</ref>
+* Suspected cases of skeletal dysplasia may be evaluated on radiography.
+* X-ray findings shows metaphyseal ends to be abnormal and appear as scalloped, irregular surfaces that may contain cystic areas.<ref name="pmid1437368">{{cite journal |vauthors=Mäkitie O, Marttinen E, Kaitila I |title=Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients |journal=Pediatr Radiol |volume=22 |issue=6 |pages=434–9 |date=1992 |pmid=1437368 |doi= |url=}}</ref>
+* Definitive diagnosis is made by genetic analysis of the RMRP gene.
-==Schimke Syndrome==
+==Schimke Immuno-osseous dysplasia (SIOD)==
-* Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive spondylo-epiphyseal dysplasia Schimke immunoosseous dysplasia (SIOD) is caused by homozygous or compound heterozygous mutation in the SMARCAL1 gene on chromosome 2q25.
+* SMARCAL1 gene is located on chromosome 2q25.
-* Mutations in the gene encoding the chromatin remodeling protein, SMARCAL1 (SWI/SNF2-related matrix-associated, actin-dependent regulator of chromatin
+* SMARCAL1 gene encodes matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1.<ref name="pmid11799392">{{cite journal |vauthors=Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW |title=Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia |journal=Nat. Genet. |volume=30 |issue=2 |pages=215–20 |date=February 2002 |pmid=11799392 |doi=10.1038/ng821 |url=}}</ref><ref name="pmid10653321">{{cite journal |vauthors=Boerkoel CF, O'Neill S, André JL, Benke PJ, Bogdanovíć R, Bulla M, Burguet A, Cockfield S, Cordeiro I, Ehrich JH, Fründ S, Geary DF, Ieshima A, Illies F, Joseph MW, Kaitila I, Lama G, Leheup B, Ludman MD, McLeod DR, Medeira A, Milford DV, Ormälä T, Rener-Primec Z, Santava A, Santos HG, Schmidt B, Smith GC, Spranger J, Zupancic N, Weksberg R |title=Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature |journal=Eur. J. Pediatr. |volume=159 |issue=1-2 |pages=1–7 |date=2000 |pmid=10653321 |doi= |url=}}</ref>
-<ref name="pmid11799392">{{cite journal |vauthors=Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW |title=Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia |journal=Nat. Genet. |volume=30 |issue=2 |pages=215–20 |date=February 2002 |pmid=11799392 |doi=10.1038/ng821 |url=}}</ref>
+* Homozygous or compound heterozygous mutation of SMARCAL1 gene causes Schimke immuno-osseous dysplasia (SIOD).
-* it is autosomal recessive condition, which features skeletal, renal, and immune abnormalities.<ref name="pmid10653321">{{cite journal |vauthors=Boerkoel CF, O'Neill S, André JL, Benke PJ, Bogdanovíć R, Bulla M, Burguet A, Cockfield S, Cordeiro I, Ehrich JH, Fründ S, Geary DF, Ieshima A, Illies F, Joseph MW, Kaitila I, Lama G, Leheup B, Ludman MD, McLeod DR, Medeira A, Milford DV, Ormälä T, Rener-Primec Z, Santava A, Santos HG, Schmidt B, Smith GC, Spranger J, Zupancic N, Weksberg R |title=Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature |journal=Eur. J. Pediatr. |volume=159 |issue=1-2 |pages=1–7 |date=2000 |pmid=10653321 |doi= |url=}}</ref>
+* Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive disorder.<ref name="pmid11799392">{{cite journal |vauthors=Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW |title=Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia |journal=Nat. Genet. |volume=30 |issue=2 |pages=215–20 |date=February 2002 |pmid=11799392 |doi=10.1038/ng821 |url=}}</ref>
-* characterized by short stature (often with prenatal growth deficiency), spondyloepiphyseal dysplasia, defective cellular immunity, and progressive renal failure
+* It is characterized by:
+**Short stature (often with prenatal growth deficiency)
+**Spondyloepiphyseal dysplasia
+**Defective cellular immunity
+**Progressive renal failure
 * The diagnosis should be considered in patients with short stature and immunodeficiency.
 * Renal function should be assessed if the diagnosis is suspected.
 * Radiographs for the characteristic bony anomalies should be performed.
+* [[Bone marrow]] transplantation markedly improved the marrow function.<ref name="pmid11113849">{{cite journal |vauthors=Petty EM, Yanik GA, Hutchinson RJ, Alter BP, Schmalstieg FC, Levine JE, Ginsburg D, Robillard JE, Castle VP |title=Successful bone marrow transplantation in a patient with Schimke immuno-osseous dysplasia |journal=J. Pediatr. |volume=137 |issue=6 |pages=882–6 |date=December 2000 |pmid=11113849 |doi=10.1067/mpd.2000.109147 |url=}}</ref><ref name="pmid11113849">{{cite journal |vauthors=Petty EM, Yanik GA, Hutchinson RJ, Alter BP, Schmalstieg FC, Levine JE, Ginsburg D, Robillard JE, Castle VP |title=Successful bone marrow transplantation in a patient with Schimke immuno-osseous dysplasia |journal=J. Pediatr. |volume=137 |issue=6 |pages=882–6 |date=December 2000 |pmid=11113849 |doi=10.1067/mpd.2000.109147 |url=}}</ref>
-==MYSM1 deficiency !==
+==MYSM1 deficiency ==
-* MYSM1 gene is located on 1p32.1
+* MYSM1 gene is located on chromosome 1p32.1.
-* Myb-like, SWIRM, and MPN domain 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination<ref name="pmid4098839">{{cite journal |vauthors=Nikolaev OV, Titov VN |title=[Surgical treatment of diffuse toxic goiter] |language=Russian |journal=Khirurgiia (Mosk) |volume=46 |issue=4 |pages=121–7 |date=April 1970 |pmid=4098839 |doi= |url=}}</ref>
+* MYSM1 gene encodes a deubiquitinase which  is involved in regulation of [[trancription]] and mediates [[histone deubiquitination]].<ref name="pmid4098839">{{cite journal |vauthors=Nikolaev OV, Titov VN |title=[Surgical treatment of diffuse toxic goiter] |language=Russian |journal=Khirurgiia (Mosk) |volume=46 |issue=4 |pages=121–7 |date=April 1970 |pmid=4098839 |doi= |url=}}</ref>
-* Its deficiency leads to Bone marrow failure syndrome 4.
+* MYSM1 deficiency leads to bone marrow failure syndrome 4.
-* MYSM1 deficiency is associated with developmental aberrations, progressive Bone maarow failure with myelodysplastic features, and increased susceptibility to genotoxic stress.
+* MYSM1 deficiency is inherited as an [[Autosomal recessive disorder|autosomal recessive]] pattern.<ref name="pmid24288411">{{cite journal |vauthors=Alsultan A, Shamseldin HE, Osman ME, Aljabri M, Alkuraya FS |title=MYSM1 is mutated in a family with transient transfusion-dependent anemia, mild thrombocytopenia, and low NK- and B-cell counts |journal=Blood |volume=122 |issue=23 |pages=3844–5 |date=November 2013 |pmid=24288411 |doi=10.1182/blood-2013-09-527127 |url=}}</ref><ref name="pmid28115216">{{cite journal |vauthors=Bahrami E, Witzel M, Racek T, Puchałka J, Hollizeck S, Greif-Kohistani N, Kotlarz D, Horny HP, Feederle R, Schmidt H, Sherkat R, Steinemann D, Göhring G, Schlegelbeger B, Albert MH, Al-Herz W, Klein C |title=Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations |journal=J. Allergy Clin. Immunol. |volume=140 |issue=4 |pages=1112–1119 |date=October 2017 |pmid=28115216 |doi=10.1016/j.jaci.2016.10.053 |url=}}</ref>
-* Hematopoiteic stem cell transplant is a curative therapy for patients with MYSM1 deficiency.
+* MYSM1 deficiency is associated with:
+**Developmental aberrations
+**Progressive bone marrow failure with [[myelodysplastic]] features
+**Increased susceptibility to [[genotoxic]] stress
+* Hematopoietic stem cell transplant is a curative therapy.
 ==MOPD1 deficiency==
-* akaTaybi-Linder syndrome
+* MOPD1 stands for [[microcephalic osteodysplastic primordial dwarfism type 1]].
-* RNU4ATAC gene ,encoding a small nuclear RNA (snRNA) component of the U12-dependent(minor) spliceosome on chromosome 2q14.
+* MOPD1 deficiency, also known as [[Taybi-Linder syndrome]], caused by mutations of RNU4ATAC gene.
-* It is caused by mutations in the RNU4ATAC gene and is inherited in an autosomal recessive manner
+* RNU4ATAC gene encodes a small nuclear [[RNA]] (snRNA) component of the U12-dependent spliceosome on chromosome 2q14.
-* Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) is a genetic condition that is mainly characterized by intrauterine and post-natal growth retardation<ref name="pmid22302400">{{cite journal |vauthors=Pierce MJ, Morse RP |title=The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature |journal=Am. J. Med. Genet. A |volume=158A |issue=3 |pages=606–10 |date=March 2012 |pmid=22302400 |doi=10.1002/ajmg.a.33958 |url=}}</ref>
+* MOPD1 deficiency is inherited as an [[autosomal recessive]] pattern.<ref name="pmid24288411">{{cite journal |vauthors=Alsultan A, Shamseldin HE, Osman ME, Aljabri M, Alkuraya FS |title=MYSM1 is mutated in a family with transient transfusion-dependent anemia, mild thrombocytopenia, and low NK- and B-cell counts |journal=Blood |volume=122 |issue=23 |pages=3844–5 |date=November 2013 |pmid=24288411 |doi=10.1182/blood-2013-09-527127 |url=}}</ref>
-* An abnormally small head size (microcephaly); abnormal bone growth (skeletal dysplasia); distinctive facial features; and brain anomalies
+* [[Microcephalic osteodysplastic primordial dwarfism type 1]] (MOPD1) is characterized by:<ref name="pmid22302400">{{cite journal |vauthors=Pierce MJ, Morse RP |title=The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature |journal=Am. J. Med. Genet. A |volume=158A |issue=3 |pages=606–10 |date=March 2012 |pmid=22302400 |doi=10.1002/ajmg.a.33958 |url=}}</ref>
-* Diagnosis is made on the basis of the clinical and radiological phenotype, with common radiological features including short tubular bones, enlarged metaphyses, vertebral and pelvic anomalies, elongated clavicles, bowing of the long bones and cleft vertebral arches
+** [[Intrauterine Growth Retardation|Intrauterine growth retardation]]
-* There are no specific treatments for MOPD1
+**Post-natal [[growth retardation]] with the following features:
-* Treatment is supportive only.
+***Abnormally small [[head size]]
-* The prognosis is poor with most affected individuals dying within the first year of life
+***Abnormal bone growth (skeletal [[dysplasia]])
+**Distinctive [[facial features]]
+**Brain anomalies<ref name="pmid28115216">{{cite journal |vauthors=Bahrami E, Witzel M, Racek T, Puchałka J, Hollizeck S, Greif-Kohistani N, Kotlarz D, Horny HP, Feederle R, Schmidt H, Sherkat R, Steinemann D, Göhring G, Schlegelbeger B, Albert MH, Al-Herz W, Klein C |title=Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations |journal=J. Allergy Clin. Immunol. |volume=140 |issue=4 |pages=1112–1119 |date=October 2017 |pmid=28115216 |doi=10.1016/j.jaci.2016.10.053 |url=}}</ref>
+* Diagnosis is made on the basis of the clinical and radiological phenotype.
+* Common radiological features include:
+**Short tubular [[bones]]
+**Enlarged [[metaphyses]]
+**[[Vertebrae|Vertebral]] and [[pelvic]] anomalies
+**Elongated [[clavicles]]
+**Bowing the long [[bones]]
+* There are no specific treatments for MOPD1 deficiency. There is only supportive therapy.
+* The prognosis is poor, as most affected individuals die within the first year of life.
 ==EXTL3 deficiency==
-* EXTL3 stands for EXOSTOSIN-LIKE GLYCOSYLTRANSFERASE 3
+* EXTL3 stands for exostosin-like-glycosyltransferase 3.
-* EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs)
+* EXTL3 gene located on [[chromosome]] 8p21.1
-* Missense mutations in the EXTL3 gene located on chromosome 8p21.1
+* EXTL3 regulates the synthesis of [[heparan sulfate]] which is important for both [[skeletal]] development and [[hematopoiesis]].
-* Mutation of this gene leads to a syndrome called immunoskeletal dysplasia with neurodevelopmental abnormalities
+* Mutation of EXTL3 gene leads to a syndrome called immunoskeletal [[dysplasia]] with [[neurodevelopmental abnormalities]].<ref name="pmid28148688">{{cite journal |vauthors=Volpi S, Yamazaki Y, Brauer PM, van Rooijen E, Hayashida A, Slavotinek A, Sun Kuehn H, Di Rocco M, Rivolta C, Bortolomai I, Du L, Felgentreff K, Ott de Bruin L, Hayashida K, Freedman G, Marcovecchio GE, Capuder K, Rath P, Luche N, Hagedorn EJ, Buoncompagni A, Royer-Bertrand B, Giliani S, Poliani PL, Imberti L, Dobbs K, Poulain FE, Martini A, Manis J, Linhardt RJ, Bosticardo M, Rosenzweig SD, Lee H, Puck JM, Zúñiga-Pflücker JC, Zon L, Park PW, Superti-Furga A, Notarangelo LD |title=EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay |journal=J. Exp. Med. |volume=214 |issue=3 |pages=623–637 |date=March 2017 |pmid=28148688 |pmc=5339678 |doi=10.1084/jem.20161525 |url=}}</ref>
-* Affected individuals presented with variable skeletal abnormalities and neurodevelopmental defects.
-<ref name="pmid28148688">{{cite journal |vauthors=Volpi S, Yamazaki Y, Brauer PM, van Rooijen E, Hayashida A, Slavotinek A, Sun Kuehn H, Di Rocco M, Rivolta C, Bortolomai I, Du L, Felgentreff K, Ott de Bruin L, Hayashida K, Freedman G, Marcovecchio GE, Capuder K, Rath P, Luche N, Hagedorn EJ, Buoncompagni A, Royer-Bertrand B, Giliani S, Poliani PL, Imberti L, Dobbs K, Poulain FE, Martini A, Manis J, Linhardt RJ, Bosticardo M, Rosenzweig SD, Lee H, Puck JM, Zúñiga-Pflücker JC, Zon L, Park PW, Superti-Furga A, Notarangelo LD |title=EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay |journal=J. Exp. Med. |volume=214 |issue=3 |pages=623–637 |date=March 2017 |pmid=28148688 |pmc=5339678 |doi=10.1084/jem.20161525 |url=}}</ref>
-===Thymic Defects with additional congenital anomalies===
+==Digeorge Syndrome==
-==DiDeorge Syndrome==
+* [[22q11.2 deletion syndrome|DiGeorge syndrome]] is caused by a hemizygous [[deletion]] of chromosome 22q11.2 which encodes TBX1 gene.
-* Haploinsufficiency of the TBX1 gene,in particular is responsible for most of the physical malformations
+* T-box genes are [[transcription]] factors involved in the regulation of developmental processes.
-* This deletion leads to efective development of the 3rd and 4th pharyngeal pouch system
+* Chromosome 22q11.2 deletion syndrome includes [[22q11.2 deletion syndrome|DiGeorge syndrome]] and other similar syndromes such as [[velocardiofacial syndrome]].
-* Haploinsufficiency of the TBX1 gene,in particular is responsible for most of the physical malformations
+* [[22q11.2 deletion syndrome|DiGeorge syndrome]] is inherited as an [[autosomal dominant]] pattern.
-* Chromosome 22q11.2 deletion syndrome (22qDS) includes DGS and other similar syndromes, such as velocardiofacial syndrome
+* 22q11.2 deletion leads to defective development of the 3rd and 4th pharyngeal pouch system.
-* The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia, although the phenotype is variable.
+* [[22q11.2 deletion syndrome|DiGeorge syndrome]] presents with the following:<ref name="pmid21200182">{{cite journal |vauthors=McDonald-McGinn DM, Sullivan KE |title=Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) |journal=Medicine (Baltimore) |volume=90 |issue=1 |pages=1–18 |date=January 2011 |pmid=21200182 |doi=10.1097/MD.0b013e3182060469 |url=}}</ref>
-* Palatal abnormalities and developmental delay are common Immunodeficiency is common in patients with DGS and can range from recurrent sinopulmonary infections (partial DGS) to severe combined immunodeficiency (SCID; complete DGS).
+**[[Conotruncal cardiac anomalies]]
-* The severity of the immunodeficiency is The diagnosis of and evaluation for DGS should occur for any neonate with a conotruncal heart lesion, hypocalcemia, and/or cleft palaterelated to the degree of thymic hypoplasia<ref name="pmid24198816">{{cite journal |vauthors=Davies EG |title=Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia |journal=Front Immunol |volume=4 |issue= |pages=322 |date=October 2013 |pmid=24198816 |pmc=3814041 |doi=10.3389/fimmu.2013.00322 |url=}}</ref>
+**[[Hypoplastic thymus]]
-* The diagnosis of DGS is based upon reduced numbers of CD3+ T cells, combined with either characteristic clinical findings or a demonstrated deletion in chromosome 22q11.2
+**[[Hypocalcemia]]
-* Also detected by SCID newborn screening (NBS) using an assay for T cell receptor excision circles (TRECS), a biomarker of T cell development<ref name="pmid4492158">{{cite journal |vauthors=Allison SE |title=A framework for nursing action in a nurse-conducted diabetic management clinic |journal=J Nurs Adm |volume=3 |issue=4 |pages=53–60 |date=1973 |pmid=4492158 |doi= |url=}}</ref>
+**Palatal abnormalities
-* Treatment includes supplementation with vitamin D or calcium and with parathyroid hormone
+**[[Developmental delay]]
-* Thymus tissue transplantation, bone marrow transplant, stem cell transplant, or transplant of disease-fighting blood cells may be necessary.
+** T cell immunodeficiency presents with:
-* Hematopoietic cell transplantation (HCT) is a suitable, technically easier, and more readily available alternative to thymic transplantation in the patient with complete DGS who has an HLA-identical donor
+***Recurrent sinopulmonary infections
+***[[Severe combined immunodeficiency]]
+* Any neonate with a [[conotruncal heart lesion]], [[hypocalcemia]] or [[cleft palate]] should be evaluated for [[22q11.2 deletion syndrome|DiGeorge syndrome]].<ref name="pmid24198816">{{cite journal |vauthors=Davies EG |title=Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia |journal=Front Immunol |volume=4 |issue= |pages=322 |date=October 2013 |pmid=24198816 |pmc=3814041 |doi=10.3389/fimmu.2013.00322 |url=}}</ref>
+* [[22q11.2 deletion syndrome|DiGeorge syndrome]] is diagnosed by decreased numbers of [[CD3+ T cells]], combined with either characteristic clinical findings or deletion in chromosome 22q11.2.
+* T cell receptor excision circles (TRECS), a biomarker of T cell development is also used to made by diagnosis during newborn screening.<ref name="pmid4492158">{{cite journal |vauthors=Allison SE |title=A framework for nursing action in a nurse-conducted diabetic management clinic |journal=J Nurs Adm |volume=3 |issue=4 |pages=53–60 |date=1973 |pmid=4492158 |doi= |url=}}</ref>
+* [[22q11.2 deletion syndrome|DiGeorge syndrome]] should be treated with supplementation of [[vitamin D]] or [[calcium]] and with [[parathyroid hormone]].
+* [[Hematopoietic stem cell transplantation]] is the definitive treatment.<ref name="pmid21570089">{{cite journal |vauthors=Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, Marino B, Oskarsdottir S, Philip N, Sullivan K, Swillen A, Vorstman J |title=Practical guidelines for managing patients with 22q11.2 deletion syndrome |journal=J. Pediatr. |volume=159 |issue=2 |pages=332–9.e1 |date=August 2011 |pmid=21570089 |pmc=3197829 |doi=10.1016/j.jpeds.2011.02.039 |url=}}</ref>
 ==TBX1 deficiency==
-* TBX1 gene is located on  22q11.21
+* T-box transcription factor, TBX1 gene, also known as T-box protein 1 is located on [[chromosome]] 22q11.21.
-* T-box transcription factor TBX1 also known as T-box protein 1
+* Genes in the T-box family play important roles in the formation of [[tissues]] and [[organs]] during [[embryonic]] development.
-* The TBX1 gene provides instructions for making a protein called T-box 1
+* [[Mutations]] in the TBX1 gene leads to conotruncal anamoly face syndrome and velocardiofacial syndrome.
-* Genes in the T-box family play important roles in the formation of tissues and organs during embryonic development
-* CONOTRUNCAL ANOMALY FACE SYNDROME/VELOCARDIOFACIAL SYNDROME and DIGEORGE SYNDROME
 ==Chromosome 10p13-p14 deletion Syndrome==
-* Chromosome 10, monosomy 10p is a rare chromosomal disorder in which the end (distal) portion of the short arm (p) of chromosome 10 is missing (deleted or monosomic)
+* Chromosome 10p13-p14 deletion syndrome is a rare disease in which the end portion of the short arm (p) of [[chromosome]] 10 is missing.
-* The severity of symptoms may be variable, depending upon the exact size or location of the deletion on chromosome 10p.
+* The severity of symptoms is variable, depending upon the exact size or location of the [[deletion]] on chromosome 10p.
-* Clinical features often include severe intellectual disability; postnatal growth retardation, distinctive malformations of the skull and craniofacial region.
+* Clinical features often include followings:
-* A short neck and/or congenital heart defects are also present.
+**Severe [[mental retardation]]
-* Monosomy 10p is also frequently associated with growth delays after birth, resulting in short stature
+**[[Postnatal growth retardation]] resulting in [[short stature]]
+**Distinctive malformations of the skull and craniofacial region
-* Several cases have also been reported in which affected individuals have some features of DiGeorge syndrome (DGS)
+**A [[short neck]]
-* A diagnosis of chromosome 10, monosomy 10p may be suggested before birth (prenatally) by tests such as amniocentesis or chorionic villus sampling (CVS)
+**[[Congenital heart defects]]
+* Affected individuals have some features of [[DiGeorge syndrome]].
+* Chromosome 10p13-p14 deletion syndrome is diagnosed prenatally by tests such as [[amniocentesis]] or [[chorionic villus sampling]].
 * The treatment of affected individuals is symptomatic and supportive.
 ==CHARGE Syndrome==
-* CHARGE syndrome stands for CHARGE ASSOCIATION--COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES
+* CHARGE syndrome is caused by [[heterozygous]] [[mutation]] in the CHD7 gene located on chromosome 8q12.
-* Caused by heterozygous mutation in the CHD7 on chromosome 8q12.
+* CHARGE Syndrome is inherited as an [[autosomal dominant]] pattern.
-* CHD7 is essential for the formation of multipotent migratory neural crest, a transient cell population that is ectodermal in origin but undergoes a major transcriptional reprogramming event to acquire a remarkably broad differentiation potential and ability to migrate throughout the body, giving rise to craniofacial bones and cartilages, the peripheral nervous system, pigmentation, and cardiac structures
+* CHD7 gene is essential for the formation of [[multipotent]] migratory [[neural crest cells]]. Neural crest cells are [[ectodermal]] in origin, but undergo a major transcriptional reprogramming event and acquire a differentiation potential and ability to migrate throughout the body.
-* Inherited as an Autonsomal Dominant pattern
+* CHARGE syndrome stands for:<ref name="pmid10590394">{{cite journal |vauthors=Källén K, Robert E, Mastroiacovo P, Castilla EE, Källén B |title=CHARGE Association in newborns: a registry-based study |journal=Teratology |volume=60 |issue=6 |pages=334–43 |date=December 1999 |pmid=10590394 |doi=10.1002/(SICI)1096-9926(199912)60:6<334::AID-TERA5>3.0.CO;2-S |url=}}</ref><ref name="pmid17299439">{{cite journal |vauthors=Sanlaville D, Verloes A |title=CHARGE syndrome: an update |journal=Eur. J. Hum. Genet. |volume=15 |issue=4 |pages=389–99 |date=April 2007 |pmid=17299439 |doi=10.1038/sj.ejhg.5201778 |url=}}</ref>
-* Characterized by a pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina
+**[[Coloboma]]
+**Heart anamoly
+**[[Choanal atresia]]
+**[[Retardation]]
+**[[Genital anamolies]]
+**Ear anamolies
+== Job Syndrome ==
+* STAT3 [[gene]] stands for signal transducer and activator of [[transcription]] 3.
+* STAT3 [[gene]] is important in the [[JAK-STAT signaling]] pathway activated by [[cytokines]] such as [[IL-6]] and [[IL-2]].
+* Defects in the [[JAK-STAT]] pathway also lead to impaired [[T helper cell type 17]] (Th17) differentiation and function.
+* Defect in [[Th17]] cells function also results in decreased [[neutrophil]] proliferation and [[chemotaxis]] to the site of [[infection]].
+* [[Job syndrome]], also known as [[Hyper-IgE syndrome]], is caused by [[heterozygous]] [[mutation]] in the [[STAT3]] [[gene]] on [[chromosome]] 17q21.
+* [[Job syndrome]] is inherited as [[autosomal dominant]] pattern.
+* [[Job syndrome]] is characterized by the following:
+**Chronic [[eczema]]
+**Recurrent [[staphylococcal]] infections resulthing in cold [[abcess]]
+**Increased serum [[IgE]]
+**[[Eosinophilia]]
+**[[Skeletal]] manifestation such as:
+***Distinctive [[coarse facial appearance]]
+***Abnormal [[dentition]]
+***[[Hyperextensibility]] of the [[joints]]
+***[[Bone fractures]]
+* The diagnosis of [[job syndrome]] is based upon the presence of suggestive clinical and laboratory findings, and confirmed by [[molecular testing]] of STAT3 [[gene]].
+* Management of [[jobs syndrome]] is focused on skin care and [[antimicrobial]] prophylaxis.
-== Hyper-IgE syndromes ==
+== Comel Netherton syndrome ==
+* Comel Netherton syndrome is caused by [[mutations]] in the serine protease inhibitor of Kazal type 5 [[gene]] (SPINK5) on [[chromosome]] 5q32.
+* SPINK5 [[gene]] encodes a multidomain serine protein kinase known as lymphoepithelial Kazal type inhibitor (LEKTI) expressed in [[epithelial]] and [[mucosal]] surfaces.<ref name="pmid10835624">{{cite journal |vauthors=Chavanas S, Bodemer C, Rochat A, Hamel-Teillac D, Ali M, Irvine AD, Bonafé JL, Wilkinson J, Taïeb A, Barrandon Y, Harper JI, de Prost Y, Hovnanian A |title=Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome |journal=Nat. Genet. |volume=25 |issue=2 |pages=141–2 |date=June 2000 |pmid=10835624 |doi=10.1038/75977 |url=}}</ref>
+* Lymphoepithelial Kazal type inhibitor directly inhibits [[kallikreins]], especially kallikrein 5 (KLK5).
+* Kallikreins are critical [[epidermal]] [[proteases]] and essential for regulating [[skin]] [[desquamation]].
+* Comel Netherton syndrome is inherited as an [[autosomal recessive]] pattern.
+* Comel Netherton syndrome is clinically characterized by the followings:<ref name="pmid13582191">{{cite journal |vauthors=NETHERTON EW |title=A unique case of trichorrhexis nodosa; bamboo hairs |journal=AMA Arch Derm |volume=78 |issue=4 |pages=483–7 |date=October 1958 |pmid=13582191 |doi= |url=}}</ref>
+**[[Congenital]] [[ichthyosiform erythroderma]]
+**[[Astrichorrhexis invaginata]] ("bamboo hair")
+**[[Atopic]] [[diathesis]]
+* [[Comel Netherton syndrome]] patients exhibit absent LEKTI staining in the [[epidermis]].
+* [[Genetic testing]] will identify a [[germline]] SPINK5 [[mutation]] and confirm the diagnosis in approximately 66 to 75 percent of cases.<ref name="pmid19487419">{{cite journal |vauthors=Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Karasuyama H |title=Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |journal=J. Exp. Med. |volume=206 |issue=6 |pages=1291–301 |date=June 2009 |pmid=19487419 |pmc=2715068 |doi=10.1084/jem.20082767 |url=}}</ref>
+* There is no specific therapy for Comel Netherton syndrome. It is mainly supportive.
-== (HIES)Job Syndrome ==
+==PGM3 deficiency==
-* Autosomal dominant hyper-IgE recurrent infection syndrome is caused by heterozygous mutation in the STAT3 gene on chromosome 17q21
+* PGM 3 stands for phosphoglucomutase3.
+* PGM3 [[gene]]  is located on [[chromosome]] 6q14.
+* [[Mutation]] of PGM3 [[gene]] leads to [[immunodeficiency-23]] (IMD23).<ref name="pmid24589341">{{cite journal |vauthors=Zhang Y, Yu X, Ichikawa M, Lyons JJ, Datta S, Lamborn IT, Jing H, Kim ES, Biancalana M, Wolfe LA, DiMaggio T, Matthews HF, Kranick SM, Stone KD, Holland SM, Reich DS, Hughes JD, Mehmet H, McElwee J, Freeman AF, Freeze HH, Su HC, Milner JD |title=Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment |journal=J. Allergy Clin. Immunol. |volume=133 |issue=5 |pages=1400–9, 1409.e1–5 |date=May 2014 |pmid=24589341 |pmc=4016982 |doi=10.1016/j.jaci.2014.02.013 |url=}}</ref>
+* PGM3 deficiency is inherited as an  [[autosomal recessive]].
+* PGM3 deficiency, also known as [[immunodeficiency-vasculitis-myoclonus syndrome]], is characterized by the following:<ref name="pmid24698316">{{cite journal |vauthors=Sassi A, Lazaroski S, Wu G, Haslam SM, Fliegauf M, Mellouli F, Patiroglu T, Unal E, Ozdemir MA, Jouhadi Z, Khadir K, Ben-Khemis L, Ben-Ali M, Ben-Mustapha I, Borchani L, Pfeifer D, Jakob T, Khemiri M, Asplund AC, Gustafsson MO, Lundin KE, Falk-Sörqvist E, Moens LN, Gungor HE, Engelhardt KR, Dziadzio M, Stauss H, Fleckenstein B, Meier R, Prayitno K, Maul-Pavicic A, Schaffer S, Rakhmanov M, Henneke P, Kraus H, Eibel H, Kölsch U, Nadifi S, Nilsson M, Bejaoui M, Schäffer AA, Smith CI, Dell A, Barbouche MR, Grimbacher B |title=Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels |journal=J. Allergy Clin. Immunol. |volume=133 |issue=5 |pages=1410–9, 1419.e1–13 |date=May 2014 |pmid=24698316 |pmc=4825677 |doi=10.1016/j.jaci.2014.02.025 |url=}}</ref><ref name="pmid24589341">{{cite journal |vauthors=Zhang Y, Yu X, Ichikawa M, Lyons JJ, Datta S, Lamborn IT, Jing H, Kim ES, Biancalana M, Wolfe LA, DiMaggio T, Matthews HF, Kranick SM, Stone KD, Holland SM, Reich DS, Hughes JD, Mehmet H, McElwee J, Freeman AF, Freeze HH, Su HC, Milner JD |title=Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment |journal=J. Allergy Clin. Immunol. |volume=133 |issue=5 |pages=1400–9, 1409.e1–5 |date=May 2014 |pmid=24589341 |pmc=4016982 |doi=10.1016/j.jaci.2014.02.013 |url=}}</ref>
+**Recurrent [[respiratory]] and [[skin]] [[infections]] beginning in early childhood
+**[[Developmental delay]]
+**[[Cognitive impairment]] of varying severity
+**[[Eczema]]
+**Increased serum [[IgE]]
-* Hyper-IgE recurrent infection syndrome is a primary immunodeficiency disorder characterized by chronic eczema, recurrent Staphylococcal infections, increased serum IgE, and eosinophilia.
-* Patients have a distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures
-* STAT3 is important in the signaling induced by multiple families of cytokines, hormones, and growth factors, although the precise mechanisms that unify the infectious, dermatologic, skeletal, and immunologic features of this disorder are not yet known
-* Laboratory abnormalities include elevated total serum IgE levels, typically ranging from 1000 to >50,000 int. units/mL, and variable eosinophilia.
-* The diagnosis of HIES is based upon the presence of suggestive clinical and laboratory findings.
-* The diagnosis can be confirmed by molecular testing.
-* Management of patients with HIES is focused on skin care, prevention of infection, prompt and complete treatment of infections, and control of pulmonary complications
-== Comel Netherton Syndrome ==
-* Rare autosomal recessive disorder of cornification caused by mutations in the serine protease inhibitor of Kazal type 5 gene (SPINK5)on chromosome 5q32.
-* SPINK5 encodes a multidomain serine protein kinase known as lymphoepithelial Kazal type inhibitor (LEKTI) expressed in epithelial and mucosal surfaces
-* Among the proteases it directly inhibits are several kallikreins, especially kallikrein 5 (KLK5). Kallikreins are critical epidermal proteases, important for regulating skin desquamation
-* It is clinically characterized by the classic triad of congenital ichthyosiform erythroderma, a specific hair shaft abnormality termed trichorrhexis invaginata ("bamboo hair"), and an atopic diathesis
-* Many NS patients exhibit absent LEKTI staining in the epidermis
-* Genetic testing will identify a germline SPINK5 mutation and confirm the diagnosis in approximately 66 to 75 percent of cases
-* There is no specific therapy for NS. it is mainly supportive The erythrodermic newborn with NS has a very high risk of potentially life-threatening complications, such as hypernatremic dehydration, sepsis, and hypothermia
-==PGM3 deficiency==
-===Dyskeratosis congenita (DKC)===
 ==Dyskeratosis congenita==
-* X-linked dyskeratosis congenita (DKCX) is caused by mutation in the DKC1 gene on chromosome Xq28
+* Dyskeratosis congenita is caused by [[mutation]] in DKC1 [[gene]] on [[chromosome]] Xq28.<ref name="pmid9888995">{{cite journal |vauthors=Hassock S, Vetrie D, Giannelli F |title=Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene |journal=Genomics |volume=55 |issue=1 |pages=21–7 |date=January 1999 |pmid=9888995 |doi=10.1006/geno.1998.5600 |url=}}</ref>
-* The disorder is caused by defects in the maintenance of telomeres
+* DKC1 [[gene]] maintains [[telomere]] length in rapidly dividing [[cells]].
-* Mutations in genes that maintain telomere length in rapidly dividing cells lead to premature cell death, senescence, or genomic instability,
+* Mutations in  DKC1 [[gene]] lead to premature [[cell]] death and senescence.<ref name="pmid10591218">{{cite journal |vauthors=Mitchell JR, Wood E, Collins K |title=A telomerase component is defective in the human disease dyskeratosis congenita |journal=Nature |volume=402 |issue=6761 |pages=551–5 |date=December 1999 |pmid=10591218 |doi=10.1038/990141 |url=}}</ref>
-* It is characterized as a triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa
+* Dyskeratosis congenita is inherited as an X-linked recessive disorder.
+* Dyskeratosis congenita is characterized by the following:<ref name="pmid18005359">{{cite journal |vauthors=Kirwan M, Dokal I |title=Dyskeratosis congenita: a genetic disorder of many faces |journal=Clin. Genet. |volume=73 |issue=2 |pages=103–12 |date=February 2008 |pmid=18005359 |doi=10.1111/j.1399-0004.2007.00923.x |url=}}</ref>
+**Abnormal [[skin]] [[pigmentation]]
+**[[Nail]] [[dystrophy]]
+**[[Leukoplakia]] of the [[oral]] [[mucosa]]
 ==COATS plus syndrome==
-* cerebroretinal microangiopathy with calcifications and cysts-1 (CRMCC1) is also known as COATS plus syndrome
+* COATS plus syndrome is also known as [[cerebroretinal]] [[microangiopathy]] with [[calcifications]] and [[cysts]]-1.
-* caused by compound heterozygous mutation in the CTC1 gene  on chromosome 17p13.
+* COATS plus syndrome is caused by [[mutation]] in the CTC1 [[gene]]  on [[chromosome]] 17p13.
-* Inherited as an Autoosomal recessive pattern
+* COATS plus syndrome is inherited as an [[autosomal recessive]] pattern.
-* characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline
+* COATS plus syndrome is characterized by followings:<ref name="pmid15002047">{{cite journal |vauthors=Crow YJ, McMenamin J, Haenggeli CA, Hadley DM, Tirupathi S, Treacy EP, Zuberi SM, Browne BH, Tolmie JL, Stephenson JB |title=Coats' plus: a progressive familial syndrome of bilateral Coats' disease, characteristic cerebral calcification, leukoencephalopathy, slow pre- and post-natal linear growth and defects of bone marrow and integument |journal=Neuropediatrics |volume=35 |issue=1 |pages=10–9 |date=February 2004 |pmid=15002047 |doi=10.1055/s-2003-43552 |url=}}</ref>
+**[[Retinal]] [[telangiectasias]] with [[exudates]]
+**[[Intracranial calcifications]]
+**[[Cerebellar]] movement disorder
+**[[Osteopenia]]
+**[[Leukoencephalopathy]]
+**[[Poor growth]]
+**[[Bone marrow failure]]
-==SAMD9==
+==SAMD9 Mutation==
-* SMD9 stands for STERILE ALPHA MOTIF DOMAIN-CONTAINING PROTEIN 9encoded by the SAMD9 gene located on 7q21.2
+* SAMD9 [[gene]] stands for sterile alpha motif domain-containing protein 9.
-* MIRAGE syndrome inherited as an Autosomal dominant pattern
+* SAMD9 [[gene]] located on 7q21.2.
-* it includes form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy
+* SAMD9 gene is encodes a [[protein]] which is localized in [[cytoplasm]] and involved in regulating [[cell]] proliferation and [[apoptosis]].
-* The condition is often fatal within the first decade of life, usually as a result of invasive infection
+* [[Mutation]] of SAMD9 [[gene]] leads to MIRAGE syndrome.
-* If the Mutation is inherited as an Autosomal Recessive Pattern then it leads to Tumoral calcinosis, familial, normophosphatemic characterized by  normophosphatemic familial tumoral calcinosis
+* MIRAGE syndrome is  inherited as an [[autosomal dominant]] pattern.
+* MIRAGE syndrome is form of syndromic [[adrenal]] [[hypoplasia]] characterized by the following:<ref name="pmid27182967">{{cite journal |vauthors=Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M, Toyoshima K, Tanaka Y, Fukuzawa R, Miyako K, Kinjo S, Ohga S, Ihara K, Inoue H, Kinjo T, Hara T, Kohno M, Yamada S, Urano H, Kitagawa Y, Tsugawa K, Higa A, Miyawaki M, Okutani T, Kizaki Z, Hamada H, Kihara M, Shiga K, Yamaguchi T, Kenmochi M, Kitajima H, Fukami M, Shimizu A, Kudoh J, Shibata S, Okano H, Miyake N, Matsumoto N, Hasegawa T |title=SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7 |journal=Nat. Genet. |volume=48 |issue=7 |pages=792–7 |date=July 2016 |pmid=27182967 |doi=10.1038/ng.3569 |url=}}</ref>
+**[[Myelodysplasia]]
+**[[Infection]]
+**Restriction of [[growth]]
+**[[Adrenal hypoplasia]]
+**[[Genital]] phenotypes
+**[[Enteropathy]]
+* MIRAGE syndrome is often fatal within the first decade of life as a result of invasive [[infection]].
+* If the mutation is SAMD9 gene is inherited as an [[autosomal recessive]] pattern, it leads to familial [[tumoral calcinosis]]
+* Familial tumoral calcinosis is characterized by massive periarticular and [[visceral]] deposition of [[calcified]] [[tumors]].<ref name="pmid3366131">{{cite journal |vauthors=Metzker A, Eisenstein B, Oren J, Samuel R |title=Tumoral calcinosis revisited--common and uncommon features. Report of ten cases and review |journal=Eur. J. Pediatr. |volume=147 |issue=2 |pages=128–32 |date=February 1988 |pmid=3366131 |doi= |url=}}</ref>
-==SAMD9L stands for STERILE ALPHA MOTIF DOMAIN-CONTAINING PROTEIN 9-LIKE==
+==SAMD9L Mutation==
-* Located on 7q21.2
+* SAMD9L stands for sterile alpha motif domain containing [[protein]] 9-like.
-* inherited as an autosomal Dominant pattern.
+* SAMD9L [[gene]] is located on [[chromosome]] 7q21.2.
-* mutation of this gene leads to Ataxia-pancytopenia syndrome
+* [[Mutation]] of SAMD9L [[gene]] leads to ataxia-pancytopenia syndrome.<ref name="pmid27259050">{{cite journal |vauthors=Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, Sul Y, Bonkowski E, Castella M, Taniguchi T, Nickerson D, Papayannopoulou T, Bird TD, Raskind WH |title=Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L |journal=Am. J. Hum. Genet. |volume=98 |issue=6 |pages=1146–1158 |date=June 2016 |pmid=27259050 |pmc=4908176 |doi=10.1016/j.ajhg.2016.04.009 |url=}}</ref>
-* It characterized by cerebellar ataxia, variable hematologic cytopenias, and presdisposition to bone marrow failure and myeloid leukemia
+* [[Ataxia]]-[[pancytopenia]] syndrome is inherited as an [[autosomal dominant]] pattern.<ref name="pmid27259050">{{cite journal |vauthors=Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, Sul Y, Bonkowski E, Castella M, Taniguchi T, Nickerson D, Papayannopoulou T, Bird TD, Raskind WH |title=Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L |journal=Am. J. Hum. Genet. |volume=98 |issue=6 |pages=1146–1158 |date=June 2016 |pmid=27259050 |pmc=4908176 |doi=10.1016/j.ajhg.2016.04.009 |url=}}</ref>
+* Ataxia-pancytopenia syndrome is characterized by the following:
+**[[Cerebellar]] [[ataxia]]
+**Variable hematologic [[cytopenias]]
+**[[Bone marrow]] failure
+**Myeloid leukemia
 ==Transcobalmin 2 deficiency==
-* TRANSCOBALAMIN II
+* Transcobalmin 2 deficiency is caused by [[mutation]] in TCN2 [[gene]].
-* TCN2 gene is located on chromosome  22q12.2
+* TCN2 [[gene]] is located on [[chromosome]] 22q12.2.
-* The TCN2 gene encodes transcobalamin II (TC II), a plasma globulin that acts as the primary transport protein for vitamin B12
+* The TCN2 [[gene]] encodes transcobalamin II which is a [[plasma]] [[globulin]] that acts as the primary transport [[protein]] for [[vitamin B12]].
-* Transcobalamin is also called as VITAMIN B12-BINDING PROTEIN 2
+* Transcobalmin 2 is also called as vitamin B12 binding protein 2.
-* TC II as well as intrinsic factor (609342) is required for transport of cobalamin from the intestine to the blood
+* Transcobalamin 2, as well as [[intrinsic factor]], is required for transportation of [[cobalamin]] from the [[intestine]] to the [[blood]].
-* Mutation of this gene leads to TCN 2 deficiency which is inherited as an Autosomal Recessive pattern
+* Transcobalmin 2 deficiency is inherited as an [[autosomal recessive]] pattern.
-* It is characterized with onset in early infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia.
+* Transcobalmin 2 deficiency is characterized by the following:<ref name="pmid19373259">{{cite journal |vauthors=Häberle J, Pauli S, Berning C, Koch HG, Linnebank M |title=TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations |journal=J. Hum. Genet. |volume=54 |issue=6 |pages=331–4 |date=June 2009 |pmid=19373259 |doi=10.1038/jhg.2009.34 |url=}}</ref>
-* Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea.
+**[[Failure to thrive]]
-* Treatment with cobalamin results in clinical improvement, but the untreated disorder may result in mental retardation and neurologic abnormalities
+**[[Megaloblastic anemia]]
+**[[Pancytopenia]]
-==Deficiency causing hereditary folate malabsorption==
+**[[Methylmalonic aciduria]]
-* hereditary folate malabsorption is caused by homozygous or compound heterozygous mutation in the SLC46A1 gene (611672) on chromosome 17q11.
+**[[Recurrent infections]]
-* Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth.
+**[[Mental retardation]]
-* Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits.
+**[[Neurologic]] abnormalities
-* Treatment with folate supplementation results in resolution of the signs and symptoms.
+* Definitive treatment is [[cobalamin]] supplement.
-* The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system
-==Methylene-tetrahydrofolate-dehydrogenase 1 deficiency==
+==Hereditary Folate Malabsorption==
+* Hereditary folate malabsorption is caused by [[mutation]] of SLC46A1 [[gene]].
+* SLC46A1 [[gene]] is located on [[chromosome]] 17q11.
+* Hereditary folate malabsorption is an [[autosomal recessive]] disorder.
+* Hereditary folate malabsorption leads to impaired [[intestinal]] [[folate]] [[absorption]] and impaired [[transport]] of [[folate]] into the [[central nervous system]].
+* Hereditary folate malabsorption presents in infancy and characterized by signs and symptoms of [[folate]] deficiency.
+* Hereditary folate malabsorption presents by the following features:<ref name="pmid17129779">{{cite journal |vauthors=Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID |title=Identification of an [[intestinal]] folate transporter and the molecular basis for hereditary folate malabsorption |journal=Cell |volume=127 |issue=5 |pages=917–28 |date=December 2006 |pmid=17129779 |doi=10.1016/j.cell.2006.09.041 |url=}}</ref>
+**Low [[blood]] and [[cerebrospinal]] fluid [[folate]] levels
+**[[Megaloblastic anemia]]
+**[[Diarrhea]]
+**[[Immunodeficiency]]
+**[[Infections]]
+**[[Neurologic deficits]]
+* Definitive treatment is [[folate]] supplementation.
-* The MTHFD1 gene encodes a trifunctional protein comprising 5,10-methylenetetrahydrofolate dehydrogenase , 5,10-methenyltetrahydrofolate cyclohydrolase , and 10-formyltetrahydrofolate synthetase
+==MTHFD1 deficiency==
-* These 3 sequential reactions are involved in the interconversion of 1-carbon derivatives of tetrahydrofolate (THF) which are substrates for methionine, thymidylate, and de novo purine syntheses.
+* The MTHFD1 [[gene]] encodes a trifunctional protein comprising 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase.
-* Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is an inborn error of folate metabolite
+* These 3 sequential enzymes are involved in the interconversion of 1-carbon derivatives of tetrahydrofolate (THF) which are substrates for [[methionine]], [[thymidylate]], and de novo [[purine]] synthesis.
-* it is  is an autosomal recessive disorder
+* Mutation of MTHFD1 [[gene]] leads to combined immunodeficiency and [[megaloblastic anemia]] with or without increased [[homocysteinemia]].<ref name="pmid27707659">{{cite journal |vauthors=Ramakrishnan KA, Pengelly RJ, Gao Y, Morgan M, Patel SV, Davies EG, Ennis S, Faust SN, Williams AP |title=Precision Molecular Diagnosis Defines Specific Therapy in Combined Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency |journal=J Allergy Clin Immunol Pract |volume=4 |issue=6 |pages=1160–1166.e10 |date=2016 |pmid=27707659 |doi=10.1016/j.jaip.2016.07.014 |url=}}</ref>
-* it is characteized bymhemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, lymphopenia involving all subsets, and low T-cell receptor excision circles.
+* The MTHFD1 deficiency is inherited as an [[autosomal recessive]] disorder.<ref name="pmid21813566">{{cite journal |vauthors=Watkins D, Schwartzentruber JA, Ganesh J, Orange JS, Kaplan BS, Nunez LD, Majewski J, Rosenblatt DS |title=Novel inborn error of folate metabolism: identification by exome capture and sequencing of [[mutations]] in the MTHFD1 gene in a single proband |journal=J. Med. Genet. |volume=48 |issue=9 |pages=590–2 |date=September 2011 |pmid=21813566 |doi=10.1136/jmedgenet-2011-100286 |url=}}</ref>
-* Folinic acid and hydroxycobalamin supplementation is an effective treatment
+* The deficiency is characterized by the following:
+**[[Hemolytic uremic syndrome]]
+**[[Macrocytosis]]
+**[[Epilepsy]]
+**[[Hearing loss]]
+**[[Retinopathy]]
+**Mild [[mental retardation]]
+**[[Lymphopenia]]
+**Low T-cell receptor excision circle
+* MTHFD1 deficiency is treated by [[folinic acid]] and [[hydroxycobalamin]] supplementation.
 ==NEMO deficiency==
-* NEMO,  also known as IKBKG,  (inhibitor of kappa polypeptide gene enhancer in B cells, kinase gamma/nuclear factor-kappa B essential modulator) gene
+* NEMO stands for NF-kappa-B essential modifier.
-* IKBKG belongs to a family of NEMO-like kinases that function in numerous cell signaling pathways.
+* NEMO is encoded by a IKBKG [[gene]] on the X chromosome.
-* NEMO-like kinases specifically phosphorylate serine or threonine residues that are followed by a proline residue
+* NEMO also known as IKBKG [[gene]] (inhibitor of kappa polypeptide gene enhancer kinase gamma).<ref name="pmid14523034">{{cite journal |vauthors=Orange JS, Geha RS |title=Finding NEMO: genetic disorders of NF-[kappa]B activation |journal=J. Clin. Invest. |volume=112 |issue=7 |pages=983–5 |date=October 2003 |pmid=14523034 |pmc=200971 |doi=10.1172/JCI19960 |url=}}</ref>
-* Ectodermal dysplasia and immune deficiency-1 (EDAID1) is caused by mutation in the IKK-gamma gene (IKBKG, or NEMO; 300248) on Xq28.
+* IKBKG belongs to a family of NEMO-like kinases that function in numerous [[cell]] signaling pathways.
-* It is an X-linked recessive disorder characterized by variable ectodermal features, but most often including hypo/anhidrosis, and various immunologic and infectious phenotypes of differing severity.
+* NEMO-like kinases specifically phosphorylate serine or threonine residues that are followed by a [[proline]] residue.
-* Mutations in this gene also leads to anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema (OLEDAID).
+* [[Ectodermal]] [[dysplasia]] and [[immune deficiency]]-1 (EDAID1) is caused by [[mutation]] in the IKK-gamma gene (IKBKG or NEMO )on Xq28.
+* NEMO deficiency is inherited as an  [[X-linked recessive]] disorder.
+* NEMO deficiency is characterized by [[ectodermal]] [[dysplasia]] with [[combined immunodeficiencies]].<ref name="pmid15356572">{{cite journal |vauthors=Orange JS, Levy O, Brodeur SR, Krzewski K, Roy RM, Niemela JE, Fleisher TA, Bonilla FA, Geha RS |title=Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia |journal=J. Allergy Clin. Immunol. |volume=114 |issue=3 |pages=650–6 |date=September 2004 |pmid=15356572 |doi=10.1016/j.jaci.2004.06.052 |url=}}</ref>
 ==EDA-ID due to IKBA GOF mutation==
-* Mutations in the NFKBIA gene result in functional impairment of NFKB ), a master transcription factor required for normal activation of immune responses.
+* Mutations in the NFKBIA gene result in functional impairment of NFKB , a master [[transcription]] factor required for normal activation of [[immune]] responses.
-* Interruption of NFKB signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection
+* Interruption of NFKB signaling results in decreased production of [[proinflammatory]] [[cytokines]] and certain [[interferons]], rendering patients susceptible to [[infection]].
-* ectodermal dysplasia and immune deficiency-2 (EDAID2) is caused by heterozygous mutation in the NFKBIA gene (164008) on chromosome 14q13.
+* Ectodermal dysplasia and immune deficiency-2 (EDAID2) is caused by heterozygous [[mutation]] in the NFKBIA [[gene]] on [[chromosome]] 14q13.
-* t is inherited as an /autosomal dominant pattern
+* It is inherited as an [[autosomal dominant]] pattern
-* EDAID2 is characterized by variable features of ectodermal dysplasia (e.g., hypo/anhidrosis, sparse hair, tooth anomalies) and various immunologic and infectious phenotypes of differing severity
+* EDAID2 is characterized by variable features of [[ectodermal dysplasia]] e.g.hypo/anhidrosis, [[sparse hair]], tooth anomalies) and various [[immunologic]] and [[infectious]] phenotypes of differing severity.
 ==Purine nucleoside phosphorylase deficiency==
-* purine nucleoside phosphorylase deficiency is caused by mutation in the PNP gene
+* [[Purine nucleoside phosphorylase]] deficiency is caused by mutation in the PNP [[gene]].
-* it is one of the enzymes involved in the purine salvage pathway Defects in this enzyme lead to intracellular accumulation of metabolites, including deoxyguanosine triphosphate (dGTP), thought to be particularly toxic to thymocytes and T cells
+* [[Purine nucleoside phosphorylase]] is one of the enzymes of [[purine]] salvage pathway.
-* Rare autosomal recessive immunodeficiency disorder characterized mainly by decreased T-cell function. Some patients also have neurologic impairment
+* Defects in purine nucleoside phosphorylase enzyme lead to intracellular accumulation of metabolites that incldes [[deoxyguanosine triphosphate]] (dGTP).
-* Patients typically present in infancy to early childhood with frequent bacterial, viral, and opportunistic infections and failure to thrive.
+* Deoxyguanosine triphosphate is particularly toxic to [[T cells]].<ref name="pmid311004">{{cite journal |vauthors=Mitchell BS, Mejias E, Daddona PE, Kelley WN |title=Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=75 |issue=10 |pages=5011–4 |date=October 1978 |pmid=311004 |pmc=336252 |doi= |url=}}</ref>
-* It also presents with progressive neurologic symptoms and autoimmune disease
+* Purine nucleoside phosphorylase deficiency is [[autosomal recessive]] disorder.
-* Low serum uric acid associated with T cell deficiency is highly suggestive of PNP deficiency, and the diagnosis should then be confirmed by measurement of PNP enzyme activity
+* Purine nucleoside phosphorylase deficiency is characterized mainly by decreased T-cell function.
-* The only curative procedure for PNP deficiency is a hematopoietic stem cell transplantation
+* Patients typically present in infancy to early childhood with frequent bacterial, viral, and opportunistic infections.<ref name="pmid1384322">{{cite journal |vauthors=Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML |title=Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency |journal=Am. J. Hum. Genet. |volume=51 |issue=4 |pages=763–72 |date=October 1992 |pmid=1384322 |pmc=1682776 |doi= |url=}}</ref>
+* Purine nucleoside phosphorylase deficiency also presents with progressive neurologic symptoms which includes ataxia, developmental delay and spasticity
+* Low serum uric acid associated with T cell deficiency is highly suggestive of PNP deficiency.
+* Diagnosis of purine nucleoside phosphorylase deficiency is confirmed by measurement of PNP enzyme activity.
+* The only curative procedure for PNP deficiency is a [[hematopoietic stem cell transplantation]].
 ==ID with multiple intestinal atresias==
-* also known as FAMILIAL INTESTINAL POLYATRESIA SYNDROME
+* Also known as familial intestinal polyaterisa syndrome.
-* gastrointestinal defects and immunodeficiency syndrome (GIDID) is caused by homozygous or compound heterozygous mutation in the TTC7A gene (609332) on chromosome 2p21.
+* Mutation in the TTC7A gene leads to gastrointestinal defects and immunodeficiency syndrome.
-* autosomal recessive inheritance.
+* TTC7A gene is located on chromosome 2p21.
-* Gastrointestinal defects and immunodeficiency syndrome (GIDID) is characterized by multiple intestinal atresia, in which atresia occurs at various levels throughout the small and large intestines.
+* TT7CA stands for tetratricopeptide repeat domain 7A.
-* Surgical outcomes are poor, and the condition is usually fatal within the first month of life.
+* TTC7A protein involves in proper development andfunction of both thymic and GI epithelium.<ref name="pmid25546680">{{cite journal |vauthors=Fernandez I, Patey N, Marchand V, Birlea M, Maranda B, Haddad E, Decaluwe H, Le Deist F |title=Multiple intestinal atresia with combined immune deficiency related to TTC7A defect is a multiorgan pathology: study of a French-Canadian-based cohort |journal=Medicine (Baltimore) |volume=93 |issue=29 |pages=e327 |date=December 2014 |pmid=25546680 |pmc=4602622 |doi=10.1097/MD.0000000000000327 |url=}}</ref>
-* Some patients exhibit inflammatory bowel disease (IBD), with or without intestinal atresia, and in some cases, the intestinal features are associated with either mild or severe combined immunodeficiency
+* Gastrointestinal defects and immunodeficiency syndrome is inherited as an autosomal recessive inheritance.
+* Gastrointestinal defects and immunodeficiency syndrome is characterized by followings
+**Multiple intestinal atresia, in which atresia throughout intestines.<ref name="pmid25174867">{{cite journal |vauthors=Lemoine R, Pachlopnik-Schmid J, Farin HF, Bigorgne A, Debré M, Sepulveda F, Héritier S, Lemale J, Talbotec C, Rieux-Laucat F, Ruemmele F, Morali A, Cathebras P, Nitschke P, Bole-Feysot C, Blanche S, Brousse N, Picard C, Clevers H, Fischer A, de Saint Basile G |title=Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency |journal=J. Allergy Clin. Immunol. |volume=134 |issue=6 |pages=1354–1364.e6 |date=December 2014 |pmid=25174867 |doi=10.1016/j.jaci.2014.07.019 |url=}}</ref>
+**Combined immunodeficiency
+* Surgical outcomes are poor, and the condition is usually fatal within the first month of life.
 ==Hepatic veno-occlusive disease with immunodeficiency==
-* hepatic venoocclusive disease with immunodeficiency (VODI) is caused by homozygous mutation in the SP110 gene (604457) on chromosome 2q37.
+* Hepatic venoocclusive disease with immunodeficiency is caused by mutation in the SP110 gene.
-* Hepatic venoocclusive disease with immunodeficiency syndrome (VODI) is an autosomal recessive primary immunodeficiency associated with hepatic vascular occlusion and fibrosis.
+* SP110 gene is located on chromosome 2q37.
-* The immunodeficiency is characterized by severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, and absent tissue plasma cells and  and hepatic veno-occlusive disease
+* SP10 gene encodes a protein called SP110 nuclear body protein which is involved in immuni reguation.
-* VODI is associated with an 85% mortality if unrecognized and untreated with intravenous immunoglobulin and Pneumocystis jerovici prophylaxis
+* Hepatic venoocclusive disease with immunodeficiency is an autosomal recessive disorder.
+* Hepatic venoocclusive disease is associated with hepatic vascular occlusion and fibrosis.
+* The immunodeficiency in hepatic venoocclusive disease is characterized by followings:<ref name="pmid16648851">{{cite journal |vauthors=Roscioli T, Cliffe ST, Bloch DB, Bell CG, Mullan G, Taylor PJ, Sarris M, Wang J, Donald JA, Kirk EP, Ziegler JB, Salzer U, McDonald GB, Wong M, Lindeman R, Buckley MF |title=Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease |journal=Nat. Genet. |volume=38 |issue=6 |pages=620–2 |date=June 2006 |pmid=16648851 |doi=10.1038/ng1780 |url=}}</ref>
+**Severe hypogammaglobulinemia
+**Combined T and B cell immunodeficiency
+**Absent lymph node germinal centers
+**Absent plasma cells
+* Hepatic veno-occlusive disease should be treat with intravenous immunoglobulin and pneumocystis jerovici prophylaxis.
 ==Vici Syndrome==
-* EPG5 is the human homolog of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomesrome (VICIS)
+* Vici syndrome is caused by mutation in the EPG5 gene.
-* It is caused by homozygous or compound heterozygous mutation in the EPG5 gene on chromosome 18q
+* EPG5 gene is located on chromosome 18q.
-* Autosomal recessive inheritance
+* EPG5 encodes a gene called EPG5 which stands for ectopic P-granules autophagy protein 5.
-* congenital multisystem disorder characterized by agenesis of the corpus callosum (ACC), cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency.
+* Ectopic P-granules autophagy protein 5 a key regulator in autophagy and forms autolysosomesrome.<ref name="pmid23222957">{{cite journal |vauthors=Cullup T, Kho AL, Dionisi-Vici C, Brandmeier B, Smith F, Urry Z, Simpson MA, Yau S, Bertini E, McClelland V, Al-Owain M, Koelker S, Koerner C, Hoffmann GF, Wijburg FA, ten Hoedt AE, Rogers RC, Manchester D, Miyata R, Hayashi M, Said E, Soler D, Kroisel PM, Windpassinger C, Filloux FM, Al-Kaabi S, Hertecant J, Del Campo M, Buk S, Bodi I, Goebel HH, Sewry CA, Abbs S, Mohammed S, Josifova D, Gautel M, Jungbluth H |title=Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy |journal=Nat. Genet. |volume=45 |issue=1 |pages=83–7 |date=January 2013 |pmid=23222957 |pmc=4012842 |doi=10.1038/ng.2497 |url=}}</ref>
-* Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy
+* Vici syndrome is inherited as an autosomal recessive pattern.<ref name="pmid20583151">{{cite journal |vauthors=Al-Owain M, Al-Hashem A, Al-Muhaizea M, Humaidan H, Al-Hindi H, Al-Homoud I, Al-Mogarri I |title=Vici syndrome associated with unilateral lung hypoplasia and myopathy |journal=Am. J. Med. Genet. A |volume=152A |issue=7 |pages=1849–53 |date=July 2010 |pmid=20583151 |doi=10.1002/ajmg.a.33421 |url=}}</ref>
+* Vici syndrome is characterized by followings:<ref name="pmid21965116">{{cite journal |vauthors=Finocchi A, Angelino G, Cantarutti N, Corbari M, Bevivino E, Cascioli S, Randisi F, Bertini E, Dionisi-Vici C |title=Immunodeficiency in Vici syndrome: a heterogeneous phenotype |journal=Am. J. Med. Genet. A |volume=158A |issue=2 |pages=434–9 |date=February 2012 |pmid=21965116 |doi=10.1002/ajmg.a.34244 |url=}}</ref>
+**Agenesis of the corpus callosum
+**Cataracts
+**Pigmentary defects
+**Progressive cardiomyopathy
+**Variable immunodeficiency
+**Profound psychomotor retardation
+**Hypotonia due to a myopathy
 ==HOIL1 deficiency==
-* also known as HEME-OXIDIZED IRP2 UBIQUITIN LIGASE 1
+* HOIL1 stands for heme -oxidized IRP2 ubiquitin ligase 1.
-* the alternate title for this gene is  RBCK1 ( RANBP-TYPE AND C3HC4-TYPE ZINC FINGER-CONTAINING 1)
+* HOIL1 also RBCK1 gene.
-* polyglucosan body myopathy-1 (PGBM1) is caused by homozygous or compound heterozygous mutation in the RBCK1 gene (610924) on chromosome 20p13.
+* RBCK1 gene encodes 1 of the components of the linear ubiquitin chain assembly complex(LUBAC)
-* Tth autosomal recessive inheritance
+* RBCK1 gene is located on chromosome 20p13
-* Polyglucosan body myopathy-1 is an autosomal recessive disorder characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation.
+* Mutation in the RBCK1 leads to polyglucosan body myopathy.
-* Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood
+* Polyglucosan body myopathy is inherited as autosomal recessive disorder.<ref name="pmid23798481">{{cite journal |vauthors=Nilsson J, Schoser B, Laforet P, Kalev O, Lindberg C, Romero NB, Dávila López M, Akman HO, Wahbi K, Iglseder S, Eggers C, Engel AG, Dimauro S, Oldfors A |title=Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1 |journal=Ann. Neurol. |volume=74 |issue=6 |pages=914–9 |date=December 2013 |pmid=23798481 |doi=10.1002/ana.23963 |url=}}</ref>
+* Polyglucosan body myopathy-1 is characterized by progressive proximal muscle weakness in early childhood.<ref name="pmid23104095">{{cite journal |vauthors=Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, Cepika AM, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debré M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet JC, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Israël A, Casanova JL, Picard C |title=Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency |journal=Nat. Immunol. |volume=13 |issue=12 |pages=1178–86 |date=December 2012 |pmid=23104095 |pmc=3514453 |doi=10.1038/ni.2457 |url=}}</ref>
+* Most patients with polyglucosan body myopathy-1 also develop progressive dilated cardiomyopathy.
+* Some patients with polyglucosan body myopathy also presents with severe immunodeficiency.
 ==HOIP1 deficiency==
-* alternate title is ZIBRA HOIL1-INTERACTING PROTEIN; HOIP
+* HOIP stands for Hoil 1-Interacting Protein.
-* caused by the mutation in RNF31 gene to chromosome 14q11.2.
+* HOIP1 deficiency is caused by the mutation in RNF31 gene.
-* inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis
+* RNF31 gene is located chromosome 14q11.2.
-* A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC
+* HOIP deficincy is characterized by followings:<ref name="pmid23104095">{{cite journal |vauthors=Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, Cepika AM, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debré M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet JC, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Israël A, Casanova JL, Picard C |title=Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency |journal=Nat. Immunol. |volume=13 |issue=12 |pages=1178–86 |date=December 2012 |pmid=23104095 |pmc=3514453 |doi=10.1038/ni.2457 |url=}}</ref>
+**Multiorgan autoinflammation
+**Combined immunodeficiency
+**Subclinical amylopectinosis
+**Systemic lymphangiectasia
-==Calcium Channel Defects(ORAI-1 deficiency, )==
+==Calcium Channel Defects (ORAI-1 deficiency)==
-* also known as ORAI calcium release-activated calcium modulator 1
+* ORAI1 is also known as calcium release-activated calcium modulator1 (CRAMC1).
-* primary immunodeficiency-9 (IMD9) is caused by homozygous or compound heterozygous mutation in the ORAI1 gene (610277), which encodes a subunit of the plasma membrane calcium channel CRAC, on chromosome 12q24
+* ORAI1 gene is located on chromosome 12q24.
-* Immunodeficiency-9 is an autosomal recessive disorder characterized by early onset of recurrent infections due to defective T-cell activation.
+* ORAI1 (CRAMC1) gene encodes a plasma membrane protein essential for pore-forming subunit of the Ca2+ release-activated calcium channels.
-* Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel
+* Mutation in the ORAI1 gene leads to primary immunodeficiency-9.<ref name="pmid20004786">{{cite journal |vauthors=McCarl CA, Picard C, Khalil S, Kawasaki T, Röther J, Papolos A, Kutok J, Hivroz C, Ledeist F, Plogmann K, Ehl S, Notheis G, Albert MH, Belohradsky BH, Kirschner J, Rao A, Fischer A, Feske S |title=ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia |journal=J. Allergy Clin. Immunol. |volume=124 |issue=6 |pages=1311–1318.e7 |date=December 2009 |pmid=20004786 |pmc=2829767 |doi=10.1016/j.jaci.2009.10.007 |url=}}</ref>
+* Primary immunodeficiency-9 in inherited as an autosomal recessive disorder.
+*Common manifestations of calcium channel defects include followings:
+**Recurrent infections due to defective T-cell activation
+**Congenital myopathy
+**Muscle weakness
+**Ectodermal dysplasia including soft dental enamel
+* If the mutation in the ORAI1 gene is inherited as an autosomal dominant pattern it leads to tubular aggregate myopathy-2.<ref name="pmid15452313">{{cite journal |vauthors=Shahrizaila N, Lowe J, Wills A |title=Familial myopathy with tubular aggregates associated with abnormal pupils |journal=Neurology |volume=63 |issue=6 |pages=1111–3 |date=September 2004 |pmid=15452313 |doi= |url=}}</ref>
+* Tubular aggregate myopathy-2 is characterized by muscle pain, cramping, or weakness that begins in childhood and worsens over time.<ref name="pmid27882542">{{cite journal |vauthors=Garibaldi M, Fattori F, Riva B, Labasse C, Brochier G, Ottaviani P, Sacconi S, Vizzaccaro E, Laschena F, Romero NB, Genazzani A, Bertini E, Antonini G |title=A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate myopathy and congenital miosis |journal=Clin. Genet. |volume=91 |issue=5 |pages=780–786 |date=May 2017 |pmid=27882542 |doi=10.1111/cge.12888 |url=}}</ref>
+* Tubular aggregate myopathy-2 involves build up of proteins abnormally in both type I and type II muscle fibers and forms clumps of tube-like structures called tubular aggregates
 ==STIM1 deficiency==
-* primary immunodeficiency-10 (IMD10) is caused by homozygous mutation in the STIM1 gene (605921) on chromosome 11p15
+* STM1 stands for stromal interaction molecule 1.
-* Immunodeficiency-10 is an autosomal recessive primary immunodeficiency characterized by onset of recurrent infections in childhood due to defective T- and NK-cell function butthe severity is variable
+* STIM1 gene is located on chromosome 11p15.
-* Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta
+* STIM1 gene encode stromal interaction molecule 1
+* Stromal interaction molecule1 senses release of Ca2+ from endoplasmic reticulum and activates CRAC channels in the plasma membrane.
+* Mutation in the STIM1 gene leads to primary immunodeficiency-10.<ref name="pmid26560041">{{cite journal |vauthors=Parry DA, Holmes TD, Gamper N, El-Sayed W, Hettiarachchi NT, Ahmed M, Cook GP, Logan CV, Johnson CA, Joss S, Peers C, Prescott K, Savic S, Inglehearn CF, Mighell AJ |title=A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency |journal=J. Allergy Clin. Immunol. |volume=137 |issue=3 |pages=955–7.e8 |date=March 2016 |pmid=26560041 |pmc=4775071 |doi=10.1016/j.jaci.2015.08.051 |url=}}</ref>
+* Immunodeficiency-10 is iherited as an autosomal recessive disorder.<ref name="pmid20876309">{{cite journal |vauthors=Byun M, Abhyankar A, Lelarge V, Plancoulaine S, Palanduz A, Telhan L, Boisson B, Picard C, Dewell S, Zhao C, Jouanguy E, Feske S, Abel L, Casanova JL |title=Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma |journal=J. Exp. Med. |volume=207 |issue=11 |pages=2307–12 |date=October 2010 |pmid=20876309 |pmc=2964585 |doi=10.1084/jem.20101597 |url=}}</ref>
+* Immunodeficiency-10 is characterized by recurrent infections in childhood due to defective T- and NK-cell function.
+* Immunodeficiency-10 also have followigs:
+**Hypotonia
+**Hypohidrosis
+**Dental enamel hypoplasia consistent with amelogenesis imperfecta
-==Hennekam-lymphangiectasia-lymphedema syndrome==
+==Hennekam-lymphangiectasia-lymphedema syndrome 2==
-* Hennekam lymphangiectasia-lymphedema syndrome-2 (HKLLS2) is caused by homozygous or compound heterozygous mutation in the FAT4 gene (612411) on chromosome 4q28.
+* Hennekam lymphangiectasia-lymphedema syndrome-2 is caused by mutation in the FAT4 gene on chromosome 4q28.
-* FAT4 gene encodes a protein that is a member of a large family of protocadherins.
+* Hennekam lymphangiectasia-lymphedema syndrome-2 is inherited as an autosomal recessive pattern.<ref name="pmid24913602">{{cite journal |vauthors=Alders M, Al-Gazali L, Cordeiro I, Dallapiccola B, Garavelli L, Tuysuz B, Salehi F, Haagmans MA, Mook OR, Majoie CB, Mannens MM, Hennekam RC |title=Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome |journal=Hum. Genet. |volume=133 |issue=9 |pages=1161–7 |date=September 2014 |pmid=24913602 |doi=10.1007/s00439-014-1456-y |url=}}</ref>
-* Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. * include facial dysmorphism and cognitive impairment
+* FAT4 gene encodes a protein which is a member of a large family of protocadherins.
+* Hennekam-lymphangiectasia-lymphedema syndrome 2 is characterized by followigs:
+**Generalized lymphatic dysplasia
+**Facial dysmorphism
+**Cognitive impairment.<ref name="pmid24913602">{{cite journal |vauthors=Alders M, Al-Gazali L, Cordeiro I, Dallapiccola B, Garavelli L, Tuysuz B, Salehi F, Haagmans MA, Mook OR, Majoie CB, Mannens MM, Hennekam RC |title=Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome |journal=Hum. Genet. |volume=133 |issue=9 |pages=1161–7 |date=September 2014 |pmid=24913602 |doi=10.1007/s00439-014-1456-y |url=}}</ref>
 ==STAT5b deficiency==
-* it stands for SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 5B
+*STAT5b deficiency also known as signal transducer and activator of transcription 5B.<ref name="pmid13679528">{{cite journal |vauthors=Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG |title=Growth hormone insensitivity associated with a STAT5b mutation |journal=N. Engl. J. Med. |volume=349 |issue=12 |pages=1139–47 |date=September 2003 |pmid=13679528 |doi=10.1056/NEJMoa022926 |url=}}</ref>
-* In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators
+* STAT5 proteins are components of the common [[growth hormone]] and [[interleukin-2]] families of cytokines signaling pathway.
-* GHI caused by a homozygous missense mutation in the gene encoding signal transducer and activator transcription 5B (STAT5B), which is essential for normal signaling of the GH receptor .
+* STAT family members are phosphorylated by the receptor associated [[kinases]] in response to [[cytokines]] and [[growth factors]].
-* The patients have severe postnatal growth failure and immune dysregulation, which is probably because STAT5B also mediates signal transduction triggered by various immune ligands, such as interleukin-2 (IL2), interleukin-4 (IL4), and colony-stimulating factor 1 (CSF1)
+* STAT proteins then form homo-or heterodimers that translocate to the cell nucleus where they act as [[transcription]] activators.<ref name="pmid8887644">{{cite journal |vauthors=Wang D, Stravopodis D, Teglund S, Kitazawa J, Ihle JN |title=Naturally occurring dominant negative variants of Stat5 |journal=Mol. Cell. Biol. |volume=16 |issue=11 |pages=6141–8 |date=November 1996 |pmid=8887644 |pmc=231617 |doi= |url=}}</ref>
-* STAT5 proteins are components of the common growth hormone and interleukin 2 family of cytokines' signaling pathway
+* Growth hormone insensitivity is caused by a mutation in the STAT5B gene which is required for normal signaling of the GH receptor.<ref name="pmid17389811">{{cite journal |vauthors=Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N, Savage MO, Rosenfeld RG |title=Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene |journal=Horm. Res. |volume=68 |issue=5 |pages=218–24 |date=2007 |pmid=17389811 |doi=10.1159/000101334 |url=}}</ref>
+* Growth hormone insensitivity includes the followings:
+**Severe growth failure
+**Elevated serum concentrations of GH
+**Clinical phenotype that identical to [[congenital]] GH deficiency.<ref name="pmid15827093">{{cite journal |vauthors=Hwa V, Little B, Adiyaman P, Kofoed EM, Pratt KL, Ocal G, Berberoglu M, Rosenfeld RG |title=Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b |journal=J. Clin. Endocrinol. Metab. |volume=90 |issue=7 |pages=4260–6 |date=July 2005 |pmid=15827093 |doi=10.1210/jc.2005-0515 |url=}}</ref>
 ==Kabuki Syndrome==
-* The protein encoded by MLL2 gene (KMT2D) gene is a histone methyltransferase that methylates the Lys-4 position of histone H3.
+* Kabuki syndrome-1 (KABUK1) is caused by [[heterozygous]] mutation in the MLL2 gene (KMT2D).
-* Kabuki syndrome-1 (KABUK1) is caused by heterozygous mutation in the MLL2 gene (KMT2D
+*MLL2 gene (KMT2D) encodes [[histone]] methyltransferase which methylates the Lys-4 position of [[histone]] H3.
-* Autosomal Dominant
+* It usually inherits as an [[autosomal dominant]] pattern.
-* Kabuki syndrome is a congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form), a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy
+*Common manifestations of Kabuki syndrome include:<ref name="pmid7277096">{{cite journal |vauthors=Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T |title=Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency |journal=J. Pediatr. |volume=99 |issue=4 |pages=565–9 |date=October 1981 |pmid=7277096 |doi= |url=}}</ref><ref name="pmid11223856">{{cite journal |vauthors=Matsune K, Shimizu T, Tohma T, Asada Y, Ohashi H, Maeda T |title=Craniofacial and dental characteristics of Kabuki syndrome |journal=Am. J. Med. Genet. |volume=98 |issue=2 |pages=185–90 |date=January 2001 |pmid=11223856 |doi= |url=}}</ref><ref name="pmid12608719">{{cite journal |vauthors=Petzold D, Kratzsch E, Opitz Ch, Tinschert S |title=The Kabuki syndrome: four patients with oral abnormalities |journal=Eur J Orthod |volume=25 |issue=1 |pages=13–9 |date=February 2003 |pmid=12608719 |doi= |url=}}</ref>
+**Congenital [[mental retardation]] syndrome
+**[[Postnatal]] [[dwarfism]]
+**long palpebral fissures with eversion of the lateral third of the lower eyelids (reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form)
+**Broad and depressed nasal tip
+**Large prominent earlobes
+**[[Cleft lip and palate|Cleft]] or [[high-arched palate]]
+**[[Scoliosis]]
+**Short fifth finger
+**Persistence of fingerpads
+**Radiographic abnormalities of the [[vertebrae]], [[hands]], and [[hip]] joints
+**Recurrent [[otitis media]] in infancy
 ==References==
 {{Reflist|2}}

Combined immunodeficiency: Difference between revisions

Latest revision as of 23:01, 28 January 2019

Overview

Classification

Wiskott-Aldrich Syndrome

X-linked thrombocytopenia (XLT)

WIP Deficiency

ARPC1B Deficiency

Ataxia-telangietectasia

Nijmegen breakage Syndrome

Bloom Syndrome

PMS2 Deficiency

Immunodeficiency with Centromeric instability and Facial anomalies(ICF1, ICF2, ICF3, ICF4)

MCM4 Deficiency

RNF168 Deficiency

POLE1 deficiency

POLE2 deficiency

NSMCE3 Deficiency

ERCC6L2 (Hebo deficiency)

Ligase 1 Deficiency

GINS1 deficiency

Cartilage hair hypoplasia

Schimke Immuno-osseous dysplasia (SIOD)

MYSM1 deficiency

MOPD1 deficiency

EXTL3 deficiency

Digeorge Syndrome

TBX1 deficiency

Chromosome 10p13-p14 deletion Syndrome

CHARGE Syndrome

Job Syndrome

Comel Netherton syndrome

PGM3 deficiency

Dyskeratosis congenita

COATS plus syndrome

SAMD9 Mutation

SAMD9L Mutation

Transcobalmin 2 deficiency

Hereditary Folate Malabsorption

MTHFD1 deficiency

NEMO deficiency

EDA-ID due to IKBA GOF mutation

Purine nucleoside phosphorylase deficiency

ID with multiple intestinal atresias

Hepatic veno-occlusive disease with immunodeficiency

Vici Syndrome

HOIL1 deficiency

HOIP1 deficiency

Calcium Channel Defects (ORAI-1 deficiency)

STIM1 deficiency

Hennekam-lymphangiectasia-lymphedema syndrome 2

STAT5b deficiency

Kabuki Syndrome

References

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