Joubert syndrome: Difference between revisions
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'''''AHI1''''' | '''''AHI1''''' | ||
* JBTS3 [[gene]](''[[AHI1]])'' plays an important role in the formation of jouberin on [[chromosome]] 6q23.<ref name="pmid15060101">{{cite journal |vauthors=Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Bétard C, Barbot C, Koenig M |title=Homozygosity mapping of a third Joubert syndrome locus to 6q23 |journal=J. Med. Genet. |volume=41 |issue=4 |pages=273–7 |date=April 2004 |pmid=15060101 |pmc=1735723 |doi=10.1136/jmg.2003.014787 |url=}}</ref><ref name="pmid16453322">{{cite journal |vauthors=Valente EM, Brancati F, Silhavy JL, Castori M, Marsh SE, Barrano G, Bertini E, Boltshauser E, Zaki MS, Abdel-Aleem A, Abdel-Salam GM, Bellacchio E, Battini R, Cruse RP, Dobyns WB, Krishnamoorthy KS, Lagier-Tourenne C, Magee A, Pascual-Castroviejo I, Salpietro CD, Sarco D, Dallapiccola B, Gleeson JG |title=AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders |journal=Ann. Neurol. |volume=59 |issue=3 |pages=527–34 |date=March 2006 |pmid=16453322 |doi=10.1002/ana.20749 |url=}}</ref> | * JBTS3 [[gene]](''[[AHI1]])'' plays an important role in the formation of jouberin on [[chromosome]] 6q23.<ref name="pmid15060101">{{cite journal |vauthors=Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Bétard C, Barbot C, Koenig M |title=Homozygosity mapping of a third Joubert syndrome locus to 6q23 |journal=J. Med. Genet. |volume=41 |issue=4 |pages=273–7 |date=April 2004 |pmid=15060101 |pmc=1735723 |doi=10.1136/jmg.2003.014787 |url=}}</ref><ref name="pmid16453322">{{cite journal |vauthors=Valente EM, Brancati F, Silhavy JL, Castori M, Marsh SE, Barrano G, Bertini E, Boltshauser E, Zaki MS, Abdel-Aleem A, Abdel-Salam GM, Bellacchio E, Battini R, Cruse RP, Dobyns WB, Krishnamoorthy KS, Lagier-Tourenne C, Magee A, Pascual-Castroviejo I, Salpietro CD, Sarco D, Dallapiccola B, Gleeson JG |title=AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders |journal=Ann. Neurol. |volume=59 |issue=3 |pages=527–34 |date=March 2006 |pmid=16453322 |doi=10.1002/ana.20749 |url=}}</ref> | ||
* [[Nonsense mutation]] in the ''[[AHI1]]'' leads to truncated [[protein]] (Jouberin) and cause the [[disease]] | * [[Nonsense mutation]] in the ''[[AHI1]]'' leads to truncated [[protein]] (Jouberin) and cause the [[disease]]<ref name="pmid16155189">{{cite journal |vauthors=Parisi MA, Doherty D, Eckert ML, Shaw DW, Ozyurek H, Aysun S, Giray O, Al Swaid A, Al Shahwan S, Dohayan N, Bakhsh E, Indridason OS, Dobyns WB, Bennett CL, Chance PF, Glass IA |title=AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome |journal=J. Med. Genet. |volume=43 |issue=4 |pages=334–9 |date=April 2006 |pmid=16155189 |pmc=2563230 |doi=10.1136/jmg.2005.036608 |url=}}</ref> | ||
'''''NPHP1''''' | '''''NPHP1''''' | ||
* JBTS4 [[gene]](''[[AHI1|NPHP1]])'' on [[chromosome]] 2q13 plays an important role in the formation of nephrocystin-1 protein<ref name="pmid9326933">{{cite journal |vauthors=Hildebrandt F, Otto E, Rensing C, Nothwang HG, Vollmer M, Adolphs J, Hanusch H, Brandis M |title=A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1 |journal=Nat. Genet. |volume=17 |issue=2 |pages=149–53 |date=October 1997 |pmid=9326933 |doi=10.1038/ng1097-149 |url=}}</ref><ref name="pmid10980528">{{cite journal |vauthors=Otto E, Betz R, Rensing C, Schätzle S, Kuntzen T, Vetsi T, Imm A, Hildebrandt F |title=A deletion distinct from the classical homologous recombination of juvenile nephronophthisis type 1 (NPH1) allows exact molecular definition of deletion breakpoints |journal=Hum. Mutat. |volume=16 |issue=3 |pages=211–23 |date=September 2000 |pmid=10980528 |doi=10.1002/1098-1004(200009)16:3<211::AID-HUMU4>3.0.CO;2-Y |url=}}</ref> | * JBTS4 [[gene]](''[[AHI1|NPHP1]])'' on [[chromosome]] 2q13 plays an important role in the formation of nephrocystin-1 protein<ref name="pmid9326933">{{cite journal |vauthors=Hildebrandt F, Otto E, Rensing C, Nothwang HG, Vollmer M, Adolphs J, Hanusch H, Brandis M |title=A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1 |journal=Nat. Genet. |volume=17 |issue=2 |pages=149–53 |date=October 1997 |pmid=9326933 |doi=10.1038/ng1097-149 |url=}}</ref><ref name="pmid10980528">{{cite journal |vauthors=Otto E, Betz R, Rensing C, Schätzle S, Kuntzen T, Vetsi T, Imm A, Hildebrandt F |title=A deletion distinct from the classical homologous recombination of juvenile nephronophthisis type 1 (NPH1) allows exact molecular definition of deletion breakpoints |journal=Hum. Mutat. |volume=16 |issue=3 |pages=211–23 |date=September 2000 |pmid=10980528 |doi=10.1002/1098-1004(200009)16:3<211::AID-HUMU4>3.0.CO;2-Y |url=}}</ref> | ||
Revision as of 12:28, 13 May 2019
| Joubert syndrome | |
| ICD-10 | Q04.3 |
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| ICD-9 | 742.2 |
| DiseasesDB | 30688 |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]
Synonyms and Keywords: Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; Joubert-Boltshauser syndrome; JBTS1; CPD4; Cerebellooculorenal syndrome 1; CORS1; Joubert syndrome 1
Overview
Joubert syndrome is a rare genetic disorder that affects the areas of the cerebellar vermis and brain stem in the brain that controls balance and coordination. Joubert syndrome follows autosomal recessive pattern of inheritance. In The United States of America in order to categorise a condition as a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.
Historical perspective
- In year 1955, the first reported cases of Joubert syndrome which are partial agenesis of the vermis of the cerebellum was collected by De Haene.[1]
- In year 1969, Joubert syndrome was first discovered in in four siblings by Dr. Marie Joubert et al.[2][3]
- In year 1977, Joubert syndrome name was first suggested by Boltshauser and Isler.
- In year 1978, Friede and Boltshauser are the first to describe neuropathologic findings in one patient with joubert syndrome.[4][5]
- In year 1978, Boltshauser et al are the first first to describe two sisters who are having joubert syndrome whose parents were consanguineous.[6][7]
Classification
- Joubert syndrome may be classified according to gene location of the mutation into many subtypes of these JBTS1 and JBTS2 are the most common and important subtypes:[8][9]
| Phenotype | Location of mutation | Gene involved | Inheritance pattern |
|---|---|---|---|
| JOUBERT SYNDROME 1(JBTS1) | 9q34.3 | INPP5E | Autosomal recessive |
| JOUBERT SYNDROME 2(JBTS2) | 11q12.2 | TMEM216 | Autosomal recessive |
Pathophysiology
- It is understood that Joubert syndrome is most commonly caused by mutation in basal body genes in INPP5E and TMEM216 gene on chromosome 9q34 and 11q12.2 respectively.
- Other genes involved in developing of joubert syndrome are as follows:[10][11]
INPP5E
- JBTS1 gene(INPP5E) plays an important role in Inositol polyphosphate-5-phosphatase E pathway on chromosome 9q34.3.[12][13][14]
- Missense mutation in Inositol polyphosphate-5-phosphatase E pathway leads to truncated protein
TMEM216
- JBTS2 gene(TMEM216 ) also plays an important role in Inositol polyphosphate-5-phosphatase on chromosome 11q12.2
- The mechanism by which the mutation leads to truncated protein is unknown
AHI1
- JBTS3 gene(AHI1) plays an important role in the formation of jouberin on chromosome 6q23.[15][16]
- Nonsense mutation in the AHI1 leads to truncated protein (Jouberin) and cause the disease[17]
NPHP1
- JBTS4 gene(NPHP1) on chromosome 2q13 plays an important role in the formation of nephrocystin-1 protein[18][19]
- Missense mutation in the NPHP1 leads to truncated protein (Nephrocystin-1 protein) and cause the disease[20][21]
CEP290
- JBTS5 gene(CEP290) on chromosome12q21.3 plays an important role in the formation of centrosomal protein of 290 kDa protein
- Nonsense mutation in the CEP290 leads to truncated protein (Centrosomal protein of 290 kDa protein) and cause the disease
TMEM67/MKS3
- JBTS6 gene(TMEM67/MKS3) on chromosome 8q21.1-q22.1 plays an important role in the formation of meckelin protein
- Missense, splice mutation leads to truncated protein (meckelin protein) and cause the disease
RPGRIP1L
- JBTS7 gene(RPGRIP1L) on chromosome 16q12.2 plays an important role in the formation of RPGR-interacting protein 1-like protein
- Missense, nonsense, splice mutation leads to truncated protein (RPGR-interacting protein 1-like protein) and cause the disease
ARL13B
- JBTS7 gene(ARL13B) on chromosome 3q11.2 plays an important role in the formation of ADP-Ribosylation factor-like 13B protein
- Missense mutation leads to truncated protein (ADP-Ribosylation factor-like 13B protein) and cause the disease
CC2D2A
- JBTS7 gene(CC2D2A) on chromosome 4p15.3 plays an important role in the formation of coiled-coil and C2 Domains-containing protein 2A protein
- Missense, nonsense, splice, frame shift mutation leads to truncated protein(C2 Domains-containing protein 2A protein) and cause the disease
Presentation
The disorder is characterized by absence or underdevelopment of a part of the brain called the cerebellar vermis and a malformed brain stem (molar tooth sign). The most common features include ataxia (lack of muscle control), an abnormal breathing pattern called hypernea, sleep apnea, abnormal eye and tongue movements, and hypotonia. Other malformations such as extra fingers and toes, cleft lip or palate, tongue abnormalities, and seizures may also occur. There may be mild or moderate retardation.
Treatment
Treatment for Joubert syndrome is symptomatic and supportive. Infant stimulation and physical, occupational, and speech therapy may benefit some patients. Infants with abnormal breathing patterns should be monitored.
Prognosis
The prognosis for individuals with Joubert syndrome varies. Some patients have a mild form with minimal motor disability and good mental development, while others may have severe motor disability and moderate mental retardation.
Genetics
Multiple genes that are mutated in individuals with Joubert syndrome have been identified:
- Mutations in a gene of unknown function called AHI1 is associated with a subset of Joubert syndrome cases.
- In some rare cases of Joubert syndrome, mutations have been found in NPHP1 which is also associated with nephronophthisis, a cystic kidney disorder.
- The gene CEP290 has been associated with both Joubert syndrome and Leber's congenital amaurosis, type 10.
References
- ↑ Stoffels, C.; Babin, E. (1976). "Angiography of incomplete lobulation of the cerebellar vermis with small fourth ventricle associated with callosal hypoplasia". Neuroradiology. 11 (2): 99–102. doi:10.1007/BF00345021. ISSN 0028-3940.
- ↑ Boltshauser E, Isler W (February 1977). "Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis". Neuropadiatrie. 8 (1): 57–66. doi:10.1055/s-0028-1091505. PMID 576733.
- ↑ Boltshauser, E.; Isler, W. (2008). "Joubert Syndrome: Episodic Hyperpnea, Abnormal Eye Movements, Retardation and Ataxia, Associated with Dysplasia of the Cerebellar Vermis". Neuropediatrics. 8 (01): 57–66. doi:10.1055/s-0028-1091505. ISSN 0174-304X.
- ↑ Friede RL, Boltshauser E (December 1978). "Uncommon syndromes of cerebellar vermis aplasia. I: Joubert syndrome". Dev Med Child Neurol. 20 (6): 758–63. PMID 729929.
- ↑ Friede, R. L.; Boltshauser, E. (2008). "Uncommon Syndromes of Cerebellar Vermis Aplasia. I: Joubert Syndrome". Developmental Medicine & Child Neurology. 20 (6): 758–763. doi:10.1111/j.1469-8749.1978.tb15307.x. ISSN 0012-1622.
- ↑ Al-Gazali L, Hamamy H (2014). "Consanguinity and dysmorphology in Arabs". Hum. Hered. 77 (1–4): 93–107. doi:10.1159/000360421. PMID 25060273.
- ↑ Al-Gazali L, Ali BR (May 2010). "Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE)". Hum. Mutat. 31 (5): 505–20. doi:10.1002/humu.21232. PMID 20437613.
- ↑ Valente, Enza Maria; Marsh, Sarah E.; Castori, Marco; Dixon-Salazar, Tracy; Bertini, Enrico; Al-Gazali, Lihadh; Messer, Jean; Barbot, Clara; Woods, C. Geoffrey; Boltshauser, Eugen; Al-Tawari, Asma A.; Salpietro, Carmelo D.; Kayserili, Hulya; Sztriha, L�szl�; Gribaa, Moez; Koenig, Michel; Dallapiccola, Bruno; Gleeson, Joseph G. (2005). "Distinguishing the four genetic causes of jouberts syndrome-related disorders". Annals of Neurology. 57 (4): 513–519. doi:10.1002/ana.20422. ISSN 0364-5134. replacement character in
|first14=at position 2 (help) - ↑ Saraiva, Jorge M.; Baraitser, Michael (1992). "Joubert syndrome: A review". American Journal of Medical Genetics. 43 (4): 726–731. doi:10.1002/ajmg.1320430415. ISSN 0148-7299.
- ↑ Parisi MA (November 2009). "Clinical and molecular features of Joubert syndrome and related disorders". Am J Med Genet C Semin Med Genet. 151C (4): 326–40. doi:10.1002/ajmg.c.30229. PMC 2797758. PMID 19876931.
- ↑ Valente EM, Marsh SE, Castori M, Dixon-Salazar T, Bertini E, Al-Gazali L, Messer J, Barbot C, Woods CG, Boltshauser E, Al-Tawari AA, Salpietro CD, Kayserili H, Sztriha L, Gribaa M, Koenig M, Dallapiccola B, Gleeson JG (April 2005). "Distinguishing the four genetic causes of Jouberts syndrome-related disorders". Ann. Neurol. 57 (4): 513–9. doi:10.1002/ana.20422. PMID 15786477.
- ↑ Saar K, Al-Gazali L, Sztriha L, Rueschendorf F, Nur-E-Kamal M, Reis A, Bayoumi R (December 1999). "Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity". Am. J. Hum. Genet. 65 (6): 1666–71. doi:10.1086/302655. PMC 1288377. PMID 10577920.
- ↑ Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, Schurmans S, Dallapiccola B, Majerus PW, Valente EM, Gleeson JG (September 2009). "Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies". Nat. Genet. 41 (9): 1032–6. doi:10.1038/ng.423. PMC 2746682. PMID 19668216.
- ↑ Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compère P, Schiffmann SN, Gergely F, Riley JH, Pérez-Morga D, Woods CG, Schurmans S (September 2009). "INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse". Nat. Genet. 41 (9): 1027–31. doi:10.1038/ng.427. PMID 19668215.
- ↑ Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Bétard C, Barbot C, Koenig M (April 2004). "Homozygosity mapping of a third Joubert syndrome locus to 6q23". J. Med. Genet. 41 (4): 273–7. doi:10.1136/jmg.2003.014787. PMC 1735723. PMID 15060101.
- ↑ Valente EM, Brancati F, Silhavy JL, Castori M, Marsh SE, Barrano G, Bertini E, Boltshauser E, Zaki MS, Abdel-Aleem A, Abdel-Salam GM, Bellacchio E, Battini R, Cruse RP, Dobyns WB, Krishnamoorthy KS, Lagier-Tourenne C, Magee A, Pascual-Castroviejo I, Salpietro CD, Sarco D, Dallapiccola B, Gleeson JG (March 2006). "AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders". Ann. Neurol. 59 (3): 527–34. doi:10.1002/ana.20749. PMID 16453322.
- ↑ Parisi MA, Doherty D, Eckert ML, Shaw DW, Ozyurek H, Aysun S, Giray O, Al Swaid A, Al Shahwan S, Dohayan N, Bakhsh E, Indridason OS, Dobyns WB, Bennett CL, Chance PF, Glass IA (April 2006). "AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome". J. Med. Genet. 43 (4): 334–9. doi:10.1136/jmg.2005.036608. PMC 2563230. PMID 16155189.
- ↑ Hildebrandt F, Otto E, Rensing C, Nothwang HG, Vollmer M, Adolphs J, Hanusch H, Brandis M (October 1997). "A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1". Nat. Genet. 17 (2): 149–53. doi:10.1038/ng1097-149. PMID 9326933.
- ↑ Otto E, Betz R, Rensing C, Schätzle S, Kuntzen T, Vetsi T, Imm A, Hildebrandt F (September 2000). "A deletion distinct from the classical homologous recombination of juvenile nephronophthisis type 1 (NPH1) allows exact molecular definition of deletion breakpoints". Hum. Mutat. 16 (3): 211–23. doi:10.1002/1098-1004(200009)16:3<211::AID-HUMU4>3.0.CO;2-Y. PMID 10980528.
- ↑ Saunier S, Calado J, Benessy F, Silbermann F, Heilig R, Weissenbach J, Antignac C (March 2000). "Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis". Am. J. Hum. Genet. 66 (3): 778–89. doi:10.1086/302819. PMC 1288163. PMID 10712196.
- ↑ Konrad M, Saunier S, Heidet L, Silbermann F, Benessy F, Calado J, Le Paslier D, Broyer M, Gubler MC, Antignac C (March 1996). "Large homozygous deletions of the 2q13 region are a major cause of juvenile nephronophthisis". Hum. Mol. Genet. 5 (3): 367–71. PMID 8852662.