Jump to navigation Jump to search
Immunodeficiency Main Page
Editor-In-Chief: C. Michael Gibson, M.S., M.D.  Shyam Patel ; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.; Anum Gull M.B.B.S.; Farman Khan, MD, MRCP ; Sadaf Sharfaei M.D.
Please see Common variable immunodeficiency. There are a variety of syndromic conditions related to immunodeficiency. Some syndromic conditions are inherited.
|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|
|Ligase 1 deficiency|
- Wiskott Aldrich syndrome (WAS) is X-Linked recessive primary immunodeficiency disorder.
- The classic triad of Wiskott-Aldrich syndrome include followings:
- Recurrent infections
- WAS gene which helps in actin polymerization, signal transduction and cytoskeletal rearrangement.
- The only curative treatment for Wiskott-Aldrich syndrome is stem cell transplant.
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.
- There is a relationship between XLT and WAS as both are caused by mutations of the same gene.
- WAS gene is mutated in X linked thrombocytopenia .
- 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.
- 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).
- 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.
- 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.
- 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.
- Deficiency of ARPC1B complex leads to platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.
- Severe manisfestations of ARPC1B deficiency include followings: 
- 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.
- 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.
- Common manifestations of AT include followings:
- Neurologic abnormalities
- Progressive cerebellar ataxia
- Abnormal eye movements
- Oculomotor apraxia
- Mild to moderate cognitive impairment
- 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
- Interstitial lung disease
- Pulmonary fibrosis
- Neuromuscular abnormalities
- Respiratory muscle weakness
- Neurologic abnormalities
- Diagnostic criteria for ataxia-telangiectasia includes followings:
- 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
- Definitive diagnosis
- Diagnosis can also be made by rapid immunoblotting assay for ATM protein because its levels are greatly reduced.
- 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:
- 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.
- There is no specific treatment for NBS.
- 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).
- Bloom Syndrome is inherited as an autosomal recessive inherited disorder.
- Most common manifestations of Bloom syndrome include followings:
- Growth deficiency of prenatal onset
- Café-au-lait spots or hypopigmented skin lesions
- Excessive photosensitivity with facial lupus-like skin lesions
- Type 2 diabetes mellitus
- Predisposition to the development of all types of cancers
- Bloom syndrome is diagnosed by detecting mutations in BLM gene.
- There is no specific treatment for bloom syndrome.
- 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.
- PMS2 Deficiency is inherited as autosomal recessive pattern.
- Deficiency of PMS2 increases the risk of colorectal cancer and hereditary nonpolyposis.
Immunodeficiency with Centromeric instability and Facial anomalies(ICF1, ICF2, ICF3, ICF4)
- ICF2 is caused by mutation in the ZBTB24 gene on chromosome 6q21.
- 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:
- 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.
- 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.
- Severe cases can be treated with allogeneic hematopoietic cell transplantation.
- 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. 
- MCM4 deficiency is characterized by:
- Short stature
- Adrenal insufficiency
- NK cell deficiency which leads to recurrent viral illnesses
- MCM4 deficiency is a variant of familial glucocorticoid deficiency (FGD), an autosomal recessive form of adrenal failure.
- 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 stands for Ring finger protein 168(RNF168).
- RNF168 gene is located on chromosome 3q29.
- RNF168 gene encodes E3 ubiquitin ligase which is involved in repair of double strand DNA breaks.
- Mutation of RNF168 gene leads to RIDDLE syndrome which is inherited as an autosomal recessive pattern.
- RIDDLE syndrome is characterized by:
- Dysmorphic features
- Learning difficulties
- Short stature
- Motor control problems
- It is pathologically similar to the ataxia-telangiectasia syndrome.
- 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.
- It is characterized by:
- Facial dysmorphism
- Livedo on the skin since birth
- Short stature
- 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 stands for DNA polymerase epsilon subunit 2.
- 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:
- 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.
- LICS syndrome is inherited as an autosomal recessive pattern.
- Mutation in the NSMCE3 gene leads to LICS syndrome.
- LICS stands for:
- Lung disease
- Chromosome breakage syndrome
- Other features include:
- Defective T cells and B cell
- Acute respiratory distress syndrome in early childhood
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.
- Mutation of ERCC6L2 gene leads to bone marrow failure syndrome 2 which is inherited as an autosomal recessive pattern.
- Bone marrow failure syndrome 2 is characterized by the followings:
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.
- Mutation of LIIG1 gene leads to reclassified-variant of unknown significance formerly called as DNA ligase 1 deficiency.
- Ligase 1 deficiency is characterized by:
- Cellular hypersensitivity to DNA-damaging agents
- 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
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.
- 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
- Clinical diagnosis is made by observing fine and sometimes sparse hair in an individual with short stature and disproportionally short limbs.
- 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.
- 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.
- 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.
- 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.
- MYSM1 gene is located on chromosome 1p32.1.
- MYSM1 gene encodes a deubiquitinase which is involved in regulation of trancription and mediates histone deubiquitination.
- MYSM1 deficiency leads to bone marrow failure syndrome 4.
- MYSM1 deficiency is inherited as an autosomal recessive pattern.
- 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 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.
- Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) is characterized by:
- Intrauterine growth retardation
- Post-natal growth retardation with the following features:
- Distinctive facial features
- Brain anomalies
- Diagnosis is made on the basis of the clinical and radiological phenotype.
- Common radiological features include:
- 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 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.
- 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:
- Conotruncal cardiac anomalies
- Hypoplastic thymus
- 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.
- 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.
- DiGeorge syndrome should be treated with supplementation of vitamin D or calcium and with parathyroid hormone.
- Hematopoietic stem cell transplantation is the definitive treatment.
- 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 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:
- Heart anamoly
- Choanal atresia
- Genital anamolies
- Ear anamolies
- 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
- 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.
- 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:
- 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.
- There is no specific therapy for Comel Netherton syndrome. It is mainly supportive.
- PGM 3 stands for phosphoglucomutase3.
- PGM3 gene is located on chromosome 6q14.
- Mutation of PGM3 gene leads to immunodeficiency-23 (IMD23).
- PGM3 deficiency is inherited as an autosomal recessive.
- PGM3 deficiency, also known as immunodeficiency-vasculitis-myoclonus syndrome, is characterized by the following:
- Recurrent respiratory and skin infections beginning in early childhood
- Developmental delay
- Cognitive impairment of varying severity
- Increased serum IgE
- Dyskeratosis congenita is caused by mutation in DKC1 gene on chromosome Xq28.
- DKC1 gene maintains telomere length in rapidly dividing cells.
- Mutations in DKC1 gene lead to premature cell death and senescence.
- Dyskeratosis congenita is inherited as an X-linked recessive disorder.
- Dyskeratosis congenita is characterized by the following:
- 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:
- 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:
- Restriction of growth
- Adrenal hypoplasia
- Genital phenotypes
- 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.
- 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.
- Ataxia-pancytopenia syndrome is inherited as an autosomal dominant pattern.
- 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:
- 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:
- Low blood and cerebrospinal fluid folate levels
- Megaloblastic anemia
- 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.
- 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.
- The MTHFD1 deficiency is inherited as an autosomal recessive disorder.
- The deficiency is characterized by the following:
- Hemolytic uremic syndrome
- Hearing loss
- Mild mental retardation
- Low T-cell receptor excision circle
- MTHFD1 deficiency is treated by folinic acid and hydroxycobalamin supplementation.
- 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).
- 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.
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.
- 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.
- 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.
- 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.
- 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:
- 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 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.
- Vici syndrome is inherited as an autosomal recessive pattern.
- Vici syndrome is characterized by followings:
- Agenesis of the corpus callosum
- Pigmentary defects
- Progressive cardiomyopathy
- Variable immunodeficiency
- Profound psychomotor retardation
- Hypotonia due to a myopathy
- 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.
- Polyglucosan body myopathy-1 is characterized by progressive proximal muscle weakness in early childhood.
- Most patients with polyglucosan body myopathy-1 also develop progressive dilated cardiomyopathy.
- Some patients with polyglucosan body myopathy also presents with severe immunodeficiency.
- 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:
- 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.
- 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.
- Tubular aggregate myopathy-2 is characterized by muscle pain, cramping, or weakness that begins in childhood and worsens over time.
- 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
- 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.
- Immunodeficiency-10 is iherited as an autosomal recessive disorder.
- Immunodeficiency-10 is characterized by recurrent infections in childhood due to defective T- and NK-cell function.
- Immunodeficiency-10 also have followigs:
- 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.
- 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.
- STAT5b deficiency also known as signal transducer and activator of transcription 5B.
- 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.
- Growth hormone insensitivity is caused by a mutation in the STAT5B gene which is required for normal signaling of the GH receptor.
- Growth hormone insensitivity includes the followings:
- Severe growth failure
- Elevated serum concentrations of GH
- Clinical phenotype that identical to congenital GH deficiency.
- 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:
- 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
- Short fifth finger
- Persistence of fingerpads
- Radiographic abnormalities of the vertebrae, hands, and hip joints
- Recurrent otitis media in infancy
- ↑ Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA (December 1994). "A multiinstitutional survey of the Wiskott-Aldrich syndrome". J. Pediatr. 125 (6 Pt 1): 876–85. PMID 7996359.
- ↑ Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
- ↑ Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
- ↑ Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M (September 2007). "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)". Pediatr Hematol Oncol. 24 (6): 393–402. doi:10.1080/08880010701454404. PMID 17710656.
- ↑ 5.0 5.1 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 (April 2010). "X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options". Blood. 115 (16): 3231–8. doi:10.1182/blood-2009-09-239087. PMID 20173115.
- ↑ Medina SS, Siqueira LH, Colella MP, Yamaguti-Hayakawa GG, Duarte B, Dos Santos Vilela MM, Ozelo MC (June 2017). "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". BMC Pediatr. 17 (1): 151. doi:10.1186/s12887-017-0897-6. PMC 5480256. PMID 28641574. Vancouver style error: initials (help)
- ↑ Wada T, Itoh M, Maeba H, Toma T, Niida Y, Saikawa Y, Yachie A (April 2014). "Intermittent X-linked thrombocytopenia with a novel WAS gene mutation". Pediatr Blood Cancer. 61 (4): 746–8. doi:10.1002/pbc.24787. PMID 24115682.
- ↑ 8.0 8.1 Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG (April 1995). "X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene". Nat. Genet. 9 (4): 414–7. doi:10.1038/ng0495-414. PMID 7795648.
- ↑ Caputo O, Grosa G, Balliano G, Rocco F, Biglino G (1988). "In vitro metabolism of 2-(5-ethylpyridin-2-yl)benzimidazole". Eur J Drug Metab Pharmacokinet. 13 (1): 47–51. doi:10.1007/BF03189928. PMID 3260865.
- ↑ Pawłowski R (1991). "Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population". Hum. Hered. 41 (4): 279–80. doi:10.1159/000154013. PMID 1783416.
- ↑ 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 (March 2017). "Hematopoietic stem cell transplantation corrects WIP deficiency". J. Allergy Clin. Immunol. 139 (3): 1039–1040.e4. doi:10.1016/j.jaci.2016.08.036. PMID 27742395.
- ↑ Volkmann N, Amann KJ, Stoilova-McPhie S, Egile C, Winter DC, Hazelwood L, Heuser JE, Li R, Pollard TD, Hanein D (September 2001). "Structure of Arp2/3 complex in its activated state and in actin filament branch junctions". Science. 293 (5539): 2456–9. doi:10.1126/science.1063025. PMID 11533442.
- ↑ Kahr, Walter H. A.; Pluthero, Fred G.; Elkadri, Abdul; Warner, Neil; Drobac, Marko; Chen, Chang Hua; Lo, Richard W.; Li, Ling; Li, Ren; Li, Qi; Thoeni, Cornelia; Pan, Jie; Leung, Gabriella; Lara-Corrales, Irene; Murchie, Ryan; Cutz, Ernest; Laxer, Ronald M.; Upton, Julia; Roifman, Chaim M.; Yeung, Rae S. M.; Brumell, John H; Muise, Aleixo M (2017). "Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease". Nature Communications. 8: 14816. doi:10.1038/ncomms14816. ISSN 2041-1723.
- ↑ Kuijpers, Taco W.; Tool, Anton T.J.; van der Bijl, Ivo; de Boer, Martin; van Houdt, Michel; de Cuyper, Iris M.; Roos, Dirk; van Alphen, Floris; van Leeuwen, Karin; Cambridge, Emma L.; Arends, Mark J.; Dougan, Gordon; Clare, Simon; Ramirez-Solis, Ramiro; Pals, Steven T.; Adams, David J.; Meijer, Alexander B.; van den Berg, Timo K. (2017). "Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency". Journal of Allergy and Clinical Immunology. 140 (1): 273–277.e10. doi:10.1016/j.jaci.2016.09.061. ISSN 0091-6749.
- ↑ 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 (April 2017). "Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease". Nat Commun. 8: 14816. doi:10.1038/ncomms14816. PMC 5382316. PMID 28368018.
- ↑ Lavin MF, Shiloh Y (1997). "The genetic defect in ataxia-telangiectasia". Annu. Rev. Immunol. 15: 177–202. doi:10.1146/annurev.immunol.15.1.177. PMID 9143686.
- ↑ Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K (December 1988). "Localization of an ataxia-telangiectasia gene to chromosome 11q22-23". Nature. 336 (6199): 577–80. doi:10.1038/336577a0. PMID 3200306.
- ↑ Lewis RF, Lederman HM, Crawford TO (September 1999). "Ocular motor abnormalities in ataxia telangiectasia". Ann. Neurol. 46 (3): 287–95. PMID 10482258.
- ↑ 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 (September 2010). "Evaluation and management of pulmonary disease in ataxia-telangiectasia". Pediatr. Pulmonol. 45 (9): 847–59. doi:10.1002/ppul.21277. PMC 4151879. PMID 20583220.
- ↑ Greenberger S, Berkun Y, Ben-Zeev B, Levi YB, Barziliai A, Nissenkorn A (June 2013). "Dermatologic manifestations of ataxia-telangiectasia syndrome". J. Am. Acad. Dermatol. 68 (6): 932–6. doi:10.1016/j.jaad.2012.12.950. PMID 23360865.
- ↑ Wu JT, Book L, Sudar K (January 1981). "Serum alpha fetoprotein (AFP) levels in normal infants". Pediatr. Res. 15 (1): 50–2. PMID 6163129.
- ↑ 22.0 22.1 Butch AW, Chun HH, Nahas SA, Gatti RA (December 2004). "Immunoassay to measure ataxia-telangiectasia mutated protein in cellular lysates". Clin. Chem. 50 (12): 2302–8. doi:10.1373/clinchem.2004.039461. PMID 15486025.
- ↑ Conley ME, Notarangelo LD, Etzioni A (December 1999). "Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)". Clin. Immunol. 93 (3): 190–7. doi:10.1006/clim.1999.4799. PMID 10600329.
- ↑ 24.0 24.1 Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M (February 2012). "Nijmegen breakage syndrome (NBS)". Orphanet J Rare Dis. 7: 13. doi:10.1186/1750-1172-7-13. PMC 3314554. PMID 22373003.
- ↑ Warcoin M, Lespinasse J, Despouy G, Dubois d'Enghien C, Laugé A, Portnoï MF, Christin-Maitre S, Stoppa-Lyonnet D, Stern MH (March 2009). "Fertility defects revealing germline biallelic nonsense NBN mutations". Hum. Mutat. 30 (3): 424–30. doi:10.1002/humu.20904. PMID 19105185.
- ↑ 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 (July 2010). "High prevalence of primary ovarian insufficiency in girls and young women with Nijmegen breakage syndrome: evidence from a longitudinal study". J. Clin. Endocrinol. Metab. 95 (7): 3133–40. doi:10.1210/jc.2009-2628. PMID 20444919.
- ↑ Antoccia A, Kobayashi J, Tauchi H, Matsuura S, Komatsu K (2006). "Nijmegen breakage syndrome and functions of the responsible protein, NBS1". Genome Dyn. 1: 191–205. doi:10.1159/000092508. PMID 18724061.
- ↑ 28.0 28.1 Ellis NA, German J (1996). "Molecular genetics of Bloom's syndrome". Hum. Mol. Genet. 5 Spec No: 1457–63. PMID 8875252.
- ↑ German J (November 1993). "Bloom syndrome: a mendelian prototype of somatic mutational disease". Medicine (Baltimore). 72 (6): 393–406. PMID 8231788.
- ↑ Karalis A, Tischkowitz M, Millington GW (February 2011). "Dermatological manifestations of inherited cancer syndromes in children". Br. J. Dermatol. 164 (2): 245–56. doi:10.1111/j.1365-2133.2010.10100.x. PMID 20973772.
- ↑ 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 (June 2008). "Three new BLM gene mutations associated with Bloom syndrome". Genet. Test. 12 (2): 257–61. doi:10.1089/gte.2007.0119. PMID 18471088.
- ↑ Michels VV, Stevens JC (August 1982). "Basal cell carcinoma in a patient with intestinal polyposis". Clin. Genet. 22 (2): 80–2. PMID 7172481.
- ↑ 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 (June 2014). "Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD)". J. Med. Genet. 51 (6): 355–65. doi:10.1136/jmedgenet-2014-102284. PMID 24737826.
- ↑ Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM (September 1994). "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer". Nature. 371 (6492): 75–80. doi:10.1038/371075a0. PMID 8072530.
- ↑ 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 (January 2005). "DNMT3B mutations and DNA methylation defect define two types of ICF syndrome". Hum. Mutat. 25 (1): 56–63. doi:10.1002/humu.20113. PMID 15580563.
- ↑ 36.0 36.1 Maraschio P, Zuffardi O, Dalla Fior T, Tiepolo L (March 1988). "Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome". J. Med. Genet. 25 (3): 173–80. PMC 1015482. PMID 3351904.
- ↑ Jeanpierre M, Turleau C, Aurias A, Prieur M, Ledeist F, Fischer A, Viegas-Pequignot E (June 1993). "An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome". Hum. Mol. Genet. 2 (6): 731–5. PMID 8102570.
- ↑ Smeets DF, Moog U, Weemaes CM, Vaes-Peeters G, Merkx GF, Niehof JP, Hamers G (September 1994). "ICF syndrome: a new case and review of the literature". Hum. Genet. 94 (3): 240–6. PMID 8076938.
- ↑ Fasth A, Forestier E, Holmberg E, Holmgren G, Nordenson I, Söderström T, Wahlström J (1990). "Fragility of the centromeric region of chromosome 1 associated with combined immunodeficiency in siblings. A recessively inherited entity?". Acta Paediatr Scand. 79 (6–7): 605–12. PMID 2386052.
- ↑ 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 (February 2008). "Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome)". J. Med. Genet. 45 (2): 93–9. doi:10.1136/jmg.2007.053397. PMID 17893117.
- ↑ Gennery AR, Slatter MA, Bredius RG, Hagleitner MM, Weemaes C, Cant AJ, Lankester AC (November 2007). "Hematopoietic stem cell transplantation corrects the immunologic abnormalities associated with immunodeficiency-centromeric instability-facial dysmorphism syndrome". Pediatrics. 120 (5): e1341–4. doi:10.1542/peds.2007-0640. PMID 17908720.
- ↑ Villa A, Sinchetto F, Lanfranconi M (May 1988). "[Pathology of the myocardium and coronary vessels in sudden cardiac death. A post-mortem study of 130 cases]". Minerva Med. (in Italian). 79 (5): 373–8. PMID 3287227.
- ↑ 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 (March 2012). "Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency". J. Clin. Invest. 122 (3): 821–32. doi:10.1172/JCI61014. PMC 3287233. PMID 22354167.
- ↑ Casey JP, Nobbs M, McGettigan P, Lynch S, Ennis S (April 2012). "Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair". J. Med. Genet. 49 (4): 242–5. doi:10.1136/jmedgenet-2012-100803. PMID 22499342.
- ↑ 45.0 45.1 Eidenschenk C, Dunne J, Jouanguy E, Fourlinnie C, Gineau L, Bacq D, McMahon C, Smith O, Casanova JL, Abel L, Feighery C (April 2006). "A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8". Am. J. Hum. Genet. 78 (4): 721–7. doi:10.1086/503269. PMC 1424699. PMID 16532402.
- ↑ Devgan SS, Sanal O, Doil C, Nakamura K, Nahas SA, Pettijohn K, Bartek J, Lukas C, Lukas J, Gatti RA (September 2011). "Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia". Cell Death Differ. 18 (9): 1500–6. doi:10.1038/cdd.2011.18. PMC 3178430. PMID 21394101.
- ↑ 47.0 47.1 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 (February 2009). "The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage". Cell. 136 (3): 420–34. doi:10.1016/j.cell.2008.12.042. PMID 19203578.
- ↑ 48.0 48.1 Stewart GS, Stankovic T, Byrd PJ, Wechsler T, Miller ES, Huissoon A, Drayson MT, West SC, Elledge SJ, Taylor AM (October 2007). "RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling". Proc. Natl. Acad. Sci. U.S.A. 104 (43): 16910–5. doi:10.1073/pnas.0708408104. PMC 2040433. PMID 17940005.
- ↑ 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 (February 2013). "Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas". Nat. Genet. 45 (2): 136–44. doi:10.1038/ng.2503. PMC 3785128. PMID 23263490.
- ↑ Tamaro M, Dolzani L, Monti-Bragadin C, Sava G (May 1986). "Mutagenic activity of the dacarbazine analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt in bacterial cells". Pharmacol Res Commun. 18 (5): 491–501. PMID 3526359.
- ↑ 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 (December 2012). "Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short [[stature]] ("FILS syndrome")". J. Exp. Med. 209 (13): 2323–30. doi:10.1084/jem.20121303. PMC 3526359. PMID 23230001. URL–wikilink conflict (help)
- ↑ Li Y, Asahara H, Patel VS, Zhou S, Linn S (December 1997). "Purification, cDNA cloning, and gene mapping of the small subunit of human DNA polymerase epsilon". J. Biol. Chem. 272 (51): 32337–44. PMID 9405441.
- ↑ Miller MJ (October 1973). "Industrialization, ecology and health in the tropics". Can J Public Health. 64: Suppl: 11–6. PMID 4747780.
- ↑ 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 (August 2016). "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". J. Clin. Invest. 126 (8): 2881–92. doi:10.1172/JCI82890. PMC 4966312. PMID 27427983.
- ↑ Rickenbacher J (1968). "The importance of the regulation for the normal and abnormal development. Experimental investigations on the limb buds of chick embryos". Biol Neonat. 12 (1): 65–87. PMID 4966312.
- ↑ 56.0 56.1 56.2 Tummala H, Kirwan M, Walne AJ, Hossain U, Jackson N, Pondarre C, Plagnol V, Vulliamy T, Dokal I (February 2014). "ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function". Am. J. Hum. Genet. 94 (2): 246–56. doi:10.1016/j.ajhg.2014.01.007. PMC 3928664. PMID 24507776.
- ↑ Harrison C, Ketchen AM, Redhead NJ, O'Sullivan MJ, Melton DW (July 2002). "Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene". Cancer Res. 62 (14): 4065–74. PMID 12124343.
- ↑ Barnes DE, Tomkinson AE, Lehmann AR, Webster AD, Lindahl T (May 1992). "Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents". Cell. 69 (3): 495–503. PMID 1581963.
- ↑ 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 (May 2017). "Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency". J. Clin. Invest. 127 (5): 1991–2006. doi:10.1172/JCI90727. PMC 5409070. PMID 28414293.
- ↑ 60.0 60.1 60.2 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 (January 2001). "Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia". Cell. 104 (2): 195–203. PMID 11207361.
- ↑ MCKUSICK VA, ELDRIDGE R, HOSTETLER JA, RUANGWIT U, EGELAND JA (May 1965). "DWARFISM IN THE AMISH. II. CARTILAGE-HAIR HYPOPLASIA". Bull Johns Hopkins Hosp. 116: 285–326. PMID 14284412.
- ↑ Rider NL, Morton DH, Puffenberger E, Hendrickson CL, Robinson DL, Strauss KA (April 2009). "Immunologic and clinical features of 25 Amish patients with RMRP 70 A-->G cartilage hair hypoplasia". Clin. Immunol. 131 (1): 119–28. doi:10.1016/j.clim.2008.11.001. PMID 19150606.
- ↑ Mäkitie O, Marttinen E, Kaitila I (1992). "Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients". Pediatr Radiol. 22 (6): 434–9. PMID 1437368.
- ↑ 64.0 64.1 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 (February 2002). "Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia". Nat. Genet. 30 (2): 215–20. doi:10.1038/ng821. PMID 11799392.
- ↑ 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 (2000). "Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature". Eur. J. Pediatr. 159 (1–2): 1–7. PMID 10653321.
- ↑ 66.0 66.1 Petty EM, Yanik GA, Hutchinson RJ, Alter BP, Schmalstieg FC, Levine JE, Ginsburg D, Robillard JE, Castle VP (December 2000). "Successful bone marrow transplantation in a patient with Schimke immuno-osseous dysplasia". J. Pediatr. 137 (6): 882–6. doi:10.1067/mpd.2000.109147. PMID 11113849.
- ↑ Nikolaev OV, Titov VN (April 1970). "[Surgical treatment of diffuse toxic goiter]". Khirurgiia (Mosk) (in Russian). 46 (4): 121–7. PMID 4098839.
- ↑ 68.0 68.1 Alsultan A, Shamseldin HE, Osman ME, Aljabri M, Alkuraya FS (November 2013). "MYSM1 is mutated in a family with transient transfusion-dependent anemia, mild thrombocytopenia, and low NK- and B-cell counts". Blood. 122 (23): 3844–5. doi:10.1182/blood-2013-09-527127. PMID 24288411.
- ↑ 69.0 69.1 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 (October 2017). "Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations". J. Allergy Clin. Immunol. 140 (4): 1112–1119. doi:10.1016/j.jaci.2016.10.053. PMID 28115216.
- ↑ Pierce MJ, Morse RP (March 2012). "The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature". Am. J. Med. Genet. A. 158A (3): 606–10. doi:10.1002/ajmg.a.33958. PMID 22302400.
- ↑ 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 (March 2017). "EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay". J. Exp. Med. 214 (3): 623–637. doi:10.1084/jem.20161525. PMC 5339678. PMID 28148688.
- ↑ McDonald-McGinn DM, Sullivan KE (January 2011). "Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome)". Medicine (Baltimore). 90 (1): 1–18. doi:10.1097/MD.0b013e3182060469. PMID 21200182.
- ↑ Davies EG (October 2013). "Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia". Front Immunol. 4: 322. doi:10.3389/fimmu.2013.00322. PMC 3814041. PMID 24198816.
- ↑ Allison SE (1973). "A framework for nursing action in a nurse-conducted diabetic management clinic". J Nurs Adm. 3 (4): 53–60. PMID 4492158.
- ↑ 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 (August 2011). "Practical guidelines for managing patients with 22q11.2 deletion syndrome". J. Pediatr. 159 (2): 332–9.e1. doi:10.1016/j.jpeds.2011.02.039. PMC 3197829. PMID 21570089.
- ↑ Källén K, Robert E, Mastroiacovo P, Castilla EE, Källén B (December 1999). "CHARGE Association in newborns: a registry-based study". Teratology. 60 (6): 334–43. doi:10.1002/(SICI)1096-9926(199912)60:6<334::AID-TERA5>3.0.CO;2-S. PMID 10590394.
- ↑ Sanlaville D, Verloes A (April 2007). "CHARGE syndrome: an update". Eur. J. Hum. Genet. 15 (4): 389–99. doi:10.1038/sj.ejhg.5201778. PMID 17299439.
- ↑ 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 (June 2000). "Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome". Nat. Genet. 25 (2): 141–2. doi:10.1038/75977. PMID 10835624.
- ↑ NETHERTON EW (October 1958). "A unique case of trichorrhexis nodosa; bamboo hairs". AMA Arch Derm. 78 (4): 483–7. PMID 13582191.
- ↑ Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Karasuyama H (June 2009). "Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome". J. Exp. Med. 206 (6): 1291–301. doi:10.1084/jem.20082767. PMC 2715068. PMID 19487419.
- ↑ 81.0 81.1 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 (May 2014). "Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment". J. Allergy Clin. Immunol. 133 (5): 1400–9, 1409.e1–5. doi:10.1016/j.jaci.2014.02.013. PMC 4016982. PMID 24589341.
- ↑ 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 (May 2014). "Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels". J. Allergy Clin. Immunol. 133 (5): 1410–9, 1419.e1–13. doi:10.1016/j.jaci.2014.02.025. PMC 4825677. PMID 24698316.
- ↑ Hassock S, Vetrie D, Giannelli F (January 1999). "Mapping and characterization of the X-linked dyskeratosis congenita (DKC) gene". Genomics. 55 (1): 21–7. doi:10.1006/geno.1998.5600. PMID 9888995.
- ↑ Mitchell JR, Wood E, Collins K (December 1999). "A telomerase component is defective in the human disease dyskeratosis congenita". Nature. 402 (6761): 551–5. doi:10.1038/990141. PMID 10591218.
- ↑ Kirwan M, Dokal I (February 2008). "Dyskeratosis congenita: a genetic disorder of many faces". Clin. Genet. 73 (2): 103–12. doi:10.1111/j.1399-0004.2007.00923.x. PMID 18005359.
- ↑ Crow YJ, McMenamin J, Haenggeli CA, Hadley DM, Tirupathi S, Treacy EP, Zuberi SM, Browne BH, Tolmie JL, Stephenson JB (February 2004). "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". Neuropediatrics. 35 (1): 10–9. doi:10.1055/s-2003-43552. PMID 15002047.
- ↑ 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 (July 2016). "SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7". Nat. Genet. 48 (7): 792–7. doi:10.1038/ng.3569. PMID 27182967.
- ↑ Metzker A, Eisenstein B, Oren J, Samuel R (February 1988). "Tumoral calcinosis revisited--common and uncommon features. Report of ten cases and review". Eur. J. Pediatr. 147 (2): 128–32. PMID 3366131.
- ↑ 89.0 89.1 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 (June 2016). "Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L". Am. J. Hum. Genet. 98 (6): 1146–1158. doi:10.1016/j.ajhg.2016.04.009. PMC 4908176. PMID 27259050.
- ↑ Häberle J, Pauli S, Berning C, Koch HG, Linnebank M (June 2009). "TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations". J. Hum. Genet. 54 (6): 331–4. doi:10.1038/jhg.2009.34. PMID 19373259.
- ↑ Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID (December 2006). "Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption". Cell. 127 (5): 917–28. doi:10.1016/j.cell.2006.09.041. PMID 17129779.
- ↑ Ramakrishnan KA, Pengelly RJ, Gao Y, Morgan M, Patel SV, Davies EG, Ennis S, Faust SN, Williams AP (2016). "Precision Molecular Diagnosis Defines Specific Therapy in Combined Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency". J Allergy Clin Immunol Pract. 4 (6): 1160–1166.e10. doi:10.1016/j.jaip.2016.07.014. PMID 27707659.
- ↑ Watkins D, Schwartzentruber JA, Ganesh J, Orange JS, Kaplan BS, Nunez LD, Majewski J, Rosenblatt DS (September 2011). "Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband". J. Med. Genet. 48 (9): 590–2. doi:10.1136/jmedgenet-2011-100286. PMID 21813566.
- ↑ Orange JS, Geha RS (October 2003). "Finding NEMO: genetic disorders of NF-[kappa]B activation". J. Clin. Invest. 112 (7): 983–5. doi:10.1172/JCI19960. PMC 200971. PMID 14523034.
- ↑ Orange JS, Levy O, Brodeur SR, Krzewski K, Roy RM, Niemela JE, Fleisher TA, Bonilla FA, Geha RS (September 2004). "Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia". J. Allergy Clin. Immunol. 114 (3): 650–6. doi:10.1016/j.jaci.2004.06.052. PMID 15356572.
- ↑ Mitchell BS, Mejias E, Daddona PE, Kelley WN (October 1978). "Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells". Proc. Natl. Acad. Sci. U.S.A. 75 (10): 5011–4. PMC 336252. PMID 311004.
- ↑ Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML (October 1992). "Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency". Am. J. Hum. Genet. 51 (4): 763–72. PMC 1682776. PMID 1384322.
- ↑ Fernandez I, Patey N, Marchand V, Birlea M, Maranda B, Haddad E, Decaluwe H, Le Deist F (December 2014). "Multiple intestinal atresia with combined immune deficiency related to TTC7A defect is a multiorgan pathology: study of a French-Canadian-based cohort". Medicine (Baltimore). 93 (29): e327. doi:10.1097/MD.0000000000000327. PMC 4602622. PMID 25546680.
- ↑ 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 (December 2014). "Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency". J. Allergy Clin. Immunol. 134 (6): 1354–1364.e6. doi:10.1016/j.jaci.2014.07.019. PMID 25174867.
- ↑ 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 (June 2006). "Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease". Nat. Genet. 38 (6): 620–2. doi:10.1038/ng1780. PMID 16648851.
- ↑ 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 (January 2013). "Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy". Nat. Genet. 45 (1): 83–7. doi:10.1038/ng.2497. PMC 4012842. PMID 23222957.
- ↑ Al-Owain M, Al-Hashem A, Al-Muhaizea M, Humaidan H, Al-Hindi H, Al-Homoud I, Al-Mogarri I (July 2010). "Vici syndrome associated with unilateral lung hypoplasia and myopathy". Am. J. Med. Genet. A. 152A (7): 1849–53. doi:10.1002/ajmg.a.33421. PMID 20583151.
- ↑ Finocchi A, Angelino G, Cantarutti N, Corbari M, Bevivino E, Cascioli S, Randisi F, Bertini E, Dionisi-Vici C (February 2012). "Immunodeficiency in Vici syndrome: a heterogeneous phenotype". Am. J. Med. Genet. A. 158A (2): 434–9. doi:10.1002/ajmg.a.34244. PMID 21965116.
- ↑ 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 (December 2013). "Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1". Ann. Neurol. 74 (6): 914–9. doi:10.1002/ana.23963. PMID 23798481.
- ↑ 105.0 105.1 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 (December 2012). "Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency". Nat. Immunol. 13 (12): 1178–86. doi:10.1038/ni.2457. PMC 3514453. PMID 23104095.
- ↑ 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 (December 2009). "ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia". J. Allergy Clin. Immunol. 124 (6): 1311–1318.e7. doi:10.1016/j.jaci.2009.10.007. PMC 2829767. PMID 20004786.
- ↑ Shahrizaila N, Lowe J, Wills A (September 2004). "Familial myopathy with tubular aggregates associated with abnormal pupils". Neurology. 63 (6): 1111–3. PMID 15452313.
- ↑ 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 (May 2017). "A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate myopathy and congenital miosis". Clin. Genet. 91 (5): 780–786. doi:10.1111/cge.12888. PMID 27882542.
- ↑ 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 (March 2016). "A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency". J. Allergy Clin. Immunol. 137 (3): 955–7.e8. doi:10.1016/j.jaci.2015.08.051. PMC 4775071. PMID 26560041.
- ↑ 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 (October 2010). "Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma". J. Exp. Med. 207 (11): 2307–12. doi:10.1084/jem.20101597. PMC 2964585. PMID 20876309.
- ↑ 111.0 111.1 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 (September 2014). "Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome". Hum. Genet. 133 (9): 1161–7. doi:10.1007/s00439-014-1456-y. PMID 24913602.
- ↑ Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG (September 2003). "Growth hormone insensitivity associated with a STAT5b mutation". N. Engl. J. Med. 349 (12): 1139–47. doi:10.1056/NEJMoa022926. PMID 13679528.
- ↑ Wang D, Stravopodis D, Teglund S, Kitazawa J, Ihle JN (November 1996). "Naturally occurring dominant negative variants of Stat5". Mol. Cell. Biol. 16 (11): 6141–8. PMC 231617. PMID 8887644.
- ↑ Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N, Savage MO, Rosenfeld RG (2007). "Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene". Horm. Res. 68 (5): 218–24. doi:10.1159/000101334. PMID 17389811.
- ↑ Hwa V, Little B, Adiyaman P, Kofoed EM, Pratt KL, Ocal G, Berberoglu M, Rosenfeld RG (July 2005). "Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b". J. Clin. Endocrinol. Metab. 90 (7): 4260–6. doi:10.1210/jc.2005-0515. PMID 15827093.
- ↑ Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T (October 1981). "Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency". J. Pediatr. 99 (4): 565–9. PMID 7277096.
- ↑ Matsune K, Shimizu T, Tohma T, Asada Y, Ohashi H, Maeda T (January 2001). "Craniofacial and dental characteristics of Kabuki syndrome". Am. J. Med. Genet. 98 (2): 185–90. PMID 11223856.
- ↑ Petzold D, Kratzsch E, Opitz C, Tinschert S (February 2003). "The Kabuki syndrome: four patients with oral abnormalities". Eur J Orthod. 25 (1): 13–9. PMID 12608719. Vancouver style error: initials (help)