Details of Disease

General Information of Disease (ID: DIS7P5CO)

Disease Name Joubert syndrome
Synonyms cerebellar vermis agenesis; CPD IV; Joubert syndrome; Joubert syndrome type A; pure Joubert syndrome; Joubert-Boltshauser syndrome; classic Joubert syndrome; cerebelloparenchymal disorder IV; JBTS
Definition
Joubert syndrome (JS) is characterized by congenital malformation of the brainstem and agenesis or hypoplasia of the cerebellar vermis leading to an abnormal respiratory pattern, nystagmus, hypotonia, ataxia, and delay in achieving motor milestones.
Disease Hierarchy
DISQCXZX: Disorder of development or morphogenesis
DIS6SVEE: Syndromic disease
DIS10G4I: Ciliopathy
DIS7P5CO: Joubert syndrome
Disease Identifiers
MONDO ID
MONDO_0018772
MESH ID
C536293
UMLS CUI
C0431399
MedGen ID
98464
Orphanet ID
475
SNOMED CT ID
253175003

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 3 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
CEP290 TT3XBOV Strong Genetic Variation [1]
FGF8 TTIUF3J Strong Biomarker [2]
ITPR1 TT5HWAT Strong Genetic Variation [3]
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This Disease Is Related to 1 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
LPO DEHX1DZ Definitive CausalMutation [4]
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This Disease Is Related to 58 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
ARL13A OT979K7Z Limited Biomarker [5]
B9D2 OT5SS4P8 Limited Genetic Variation [4]
CC2D2A OTFGRGFR Limited Genetic Variation [6]
DVL1 OTD67RF1 Limited Genetic Variation [7]
KIF7 OT1J6NAW Limited Biomarker [8]
NPHP4 OTBNOA7U Limited Genetic Variation [9]
TMEM107 OT9RMLBJ Limited Genetic Variation [10]
TMEM138 OTNF4CR7 Limited Biomarker [11]
TMEM231 OTF4UYIE Limited Genetic Variation [12]
AHI1 OT8K2YWY Supportive Autosomal recessive [13]
ARL3 OT3OGOMX Supportive Autosomal recessive [14]
ARMC9 OT0MZER2 Supportive Autosomal recessive [15]
B9D1 OTWTXO75 Supportive Autosomal recessive [16]
CBY1 OTAKMUS2 Supportive Autosomal recessive [17]
CEP104 OTOLRJLH Supportive Autosomal recessive [18]
CEP120 OT1ZMRHL Supportive Autosomal recessive [19]
CEP41 OTKZTBOX Supportive Autosomal recessive [20]
CPLANE1 OTXGGNNB Supportive Autosomal recessive [21]
CSPP1 OTNX7GD4 Supportive Autosomal recessive [22]
HYLS1 OT3SW5UC Supportive Autosomal recessive [23]
INPP5E OTJF2AZ9 Supportive Autosomal recessive [24]
KATNIP OTLLA1BX Supportive Autosomal recessive [25]
KIAA0586 OTOZRC1U Supportive Autosomal recessive [26]
MKS1 OT83W5PB Supportive Autosomal recessive [16]
PIBF1 OTCBT1A1 Supportive Autosomal recessive [27]
TCTN1 OTG5KEV8 Supportive Autosomal recessive [28]
TCTN2 OTKR3I3L Supportive Autosomal recessive [29]
TMEM237 OTQEVL7L Supportive Autosomal recessive [13]
TMEM67 OTME92T5 Supportive Autosomal recessive [30]
FAM149B1 OTUBPEJ6 moderate Biomarker [31]
POC1B OTDIMIRZ moderate Biomarker [32]
SUFU OT0IRYG1 Moderate Autosomal dominant [33]
ADGRG1 OTQBB8NT Strong Genetic Variation [34]
BARHL1 OTIUTWBD Strong Biomarker [2]
CEND1 OTPHOC22 Strong Biomarker [35]
CLUAP1 OTESP4WL Strong Genetic Variation [36]
DMXL2 OTB4JWN3 Strong Genetic Variation [37]
GYS2 OTCKIUYR Strong Genetic Variation [38]
HAP1 OT6SG0JQ Strong Genetic Variation [39]
INPP5B OT0SC8W5 Strong Biomarker [40]
INVS OT8KPESR Strong Genetic Variation [41]
ITFG1 OTX0PCR3 Strong Biomarker [42]
LCA5 OTQTCUWS Strong Biomarker [43]
METTL8 OT7E09Y4 Strong Biomarker [42]
MKKS OTLF5T11 Strong Biomarker [44]
NXPH1 OTGKX860 Strong Genetic Variation [45]
OFD1 OTAZW5TK Strong Genetic Variation [46]
PDE6D OTIFVXWD Strong Biomarker [47]
RCOR1 OTREADPC Strong Genetic Variation [48]
RPGRIP1 OTABESO9 Strong Genetic Variation [49]
SYNJ1 OTTE02XC Strong Biomarker [40]
SYNJ2 OTLRHXP1 Strong Biomarker [40]
TCTN3 OTZSHERV Strong Biomarker [50]
TIPRL OTS2FZ8O Strong Biomarker [42]
TMEM216 OT1LOKOI Strong CausalMutation [51]
ARL13B OT9PYPV1 Definitive Autosomal recessive [52]
C2CD3 OTC52E7V Definitive CausalMutation [4]
IFT172 OT12DW08 Definitive CausalMutation [4]
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⏷ Show the Full List of 58 DOT(s)

References

1 Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish.PLoS One. 2019 Apr 10;14(4):e0213960. doi: 10.1371/journal.pone.0213960. eCollection 2019.
2 Search for genes involved in Joubert syndrome: evidence that one or more major loci are yet to be identified and exclusion of candidate genes EN1, EN2, FGF8, and BARHL1.Am J Med Genet. 2002 Jan 22;107(3):190-6.
3 Cerebellar vermis aplasia: patient report and exclusion of the candidate genes EN2 and ZIC1.Am J Med Genet A. 2005 Jul 15;136(2):198-200. doi: 10.1002/ajmg.a.30795.
4 Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.J Med Genet. 2015 Aug;52(8):514-22. doi: 10.1136/jmedgenet-2015-103087. Epub 2015 Jun 19.
5 Developmental expression of the zebrafish Arf-like small GTPase paralogs arl13a and arl13b.Gene Expr Patterns. 2018 Sep;29:82-87. doi: 10.1016/j.gep.2018.07.002. Epub 2018 Jul 17.
6 Novel CC2D2A compound heterozygous mutations cause Joubert syndrome.Mol Med Rep. 2017 Jan;15(1):305-308. doi: 10.3892/mmr.2016.6007. Epub 2016 Dec 7.
7 Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects.Hum Mol Genet. 2013 Apr 1;22(7):1358-72. doi: 10.1093/hmg/dds546. Epub 2013 Jan 2.
8 Clinical and experimental evidence suggest a link between KIF7 and C5orf42-related ciliopathies through Sonic Hedgehog signaling.Eur J Hum Genet. 2018 Feb;26(2):197-209. doi: 10.1038/s41431-017-0019-9. Epub 2018 Jan 10.
9 NPHP4 mutation is linked to cerebello-oculo-renal syndrome and male infertility.Clin Genet. 2014 Apr;85(4):371-5. doi: 10.1111/cge.12160. Epub 2013 Apr 26.
10 Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development.J Dent Res. 2018 Jan;97(1):108-117. doi: 10.1177/0022034517732538. Epub 2017 Sep 27.
11 Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science. 2012 Feb 24;335(6071):966-9. doi: 10.1126/science.1213506. Epub 2012 Jan 26.
12 Tectocerebellar dysraphia with occipital encephalocele: a phenotypic variant of the TMEM231 gene mutation induced Joubert syndrome.Childs Nerv Syst. 2019 Jul;35(7):1257-1261. doi: 10.1007/s00381-019-04048-9. Epub 2019 Jan 7.
13 Molecular characterization of Joubert syndrome in Saudi Arabia. Hum Mutat. 2012 Oct;33(10):1423-8. doi: 10.1002/humu.22134. Epub 2012 Jul 11.
14 ARL3 Mutations Cause Joubert Syndrome by Disrupting Ciliary Protein Composition. Am J Hum Genet. 2018 Oct 4;103(4):612-620. doi: 10.1016/j.ajhg.2018.08.015. Epub 2018 Sep 27.
15 Mutations in ARMC9, which Encodes a Basal Body Protein, Cause Joubert Syndrome in Humans and Ciliopathy Phenotypes in Zebrafish. Am J Hum Genet. 2017 Jul 6;101(1):23-36. doi: 10.1016/j.ajhg.2017.05.010. Epub 2017 Jun 15.
16 Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome. Orphanet J Rare Dis. 2014 May 5;9:72. doi: 10.1186/1750-1172-9-72.
17 Loss of CBY1 results in a ciliopathy characterized by features of Joubert syndrome. Hum Mutat. 2020 Dec;41(12):2179-2194. doi: 10.1002/humu.24127. Epub 2020 Nov 1.
18 Joubert Syndrome in French Canadians and Identification of Mutations in CEP104. Am J Hum Genet. 2015 Nov 5;97(5):744-53. doi: 10.1016/j.ajhg.2015.09.009. Epub 2015 Oct 17.
19 Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. J Med Genet. 2016 Sep;53(9):608-15. doi: 10.1136/jmedgenet-2016-103832. Epub 2016 May 6.
20 CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium. Nat Genet. 2012 Jan 15;44(2):193-9. doi: 10.1038/ng.1078.
21 Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population. Am J Hum Genet. 2012 Apr 6;90(4):693-700. doi: 10.1016/j.ajhg.2012.02.011. Epub 2012 Mar 15.
22 Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. Am J Hum Genet. 2014 Jan 2;94(1):62-72. doi: 10.1016/j.ajhg.2013.11.019. Epub 2013 Dec 19.
23 A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome. Clin Genet. 2016 Jun;89(6):739-43. doi: 10.1111/cge.12752. Epub 2016 Mar 4.
24 Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet. 2009 Sep;41(9):1032-6. doi: 10.1038/ng.423. Epub 2009 Aug 9.
25 KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome. Genome Biol. 2015 Dec 29;16:293. doi: 10.1186/s13059-015-0858-z.
26 KIAA0586 is Mutated in Joubert Syndrome. Hum Mutat. 2015 Sep;36(9):831-5. doi: 10.1002/humu.22821. Epub 2015 Jul 2.
27 An siRNA-based functional genomics screen for the?identification of regulators of ciliogenesis and ciliopathy?genes. Nat Cell Biol. 2015 Aug;17(8):1074-1087. doi: 10.1038/ncb3201. Epub 2015 Jul 13.
28 A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet. 2011 Jul 3;43(8):776-84. doi: 10.1038/ng.891.
29 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011 May 13;145(4):513-28. doi: 10.1016/j.cell.2011.04.019.
30 The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. Am J Hum Genet. 2007 Jan;80(1):186-94. doi: 10.1086/510499. Epub 2006 Nov 15.
31 Bi-allelic Mutations in FAM149B1 Cause Abnormal Primary Cilium and a Range of Ciliopathy Phenotypes in Humans. Am J Hum Genet. 2019 Apr 4;104(4):731-737. doi: 10.1016/j.ajhg.2019.02.018. Epub 2019 Mar 21.
32 Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family.Ophthalmic Genet. 2018 Jun;39(3):300-306. doi: 10.1080/13816810.2018.1430239. Epub 2018 Jan 29.
33 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
34 Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556.Neurogenetics. 2019 May;20(2):91-98. doi: 10.1007/s10048-019-00577-2. Epub 2019 Apr 13.
35 Loss of Ahi1 affects early development by impairing BM88/Cend1-mediated neuronal differentiation.J Neurosci. 2013 May 8;33(19):8172-84. doi: 10.1523/JNEUROSCI.0119-13.2013.
36 Compound heterozygous alterations in intraflagellar transport protein CLUAP1 in a child with a novel Joubert and oral-facial-digital overlap syndrome.Cold Spring Harb Mol Case Stud. 2017 Jul 5;3(4):a001321. doi: 10.1101/mcs.a001321. Print 2017 Jul.
37 Mice with a conditional deletion of Talpid3 (KIAA0586)-a model for Joubert syndrome.J Pathol. 2019 Aug;248(4):396-408. doi: 10.1002/path.5271. Epub 2019 May 16.
38 Beyond the panel: preconception screening in consanguineous couples using the TruSight One "clinical exome".Genet Med. 2019 Mar;21(3):608-612. doi: 10.1038/s41436-018-0082-9. Epub 2018 Jul 2.
39 The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions.J Biol Chem. 2013 May 10;288(19):13676-94. doi: 10.1074/jbc.M112.420786. Epub 2013 Mar 26.
40 Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E.J Cell Sci. 2017 Feb 1;130(3):563-576. doi: 10.1242/jcs.197004. Epub 2016 Dec 7.
41 Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain.PLoS Genet. 2013;9(12):e1003977. doi: 10.1371/journal.pgen.1003977. Epub 2013 Dec 5.
42 A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling.Cell Rep. 2019 Aug 13;28(7):1907-1922.e6. doi: 10.1016/j.celrep.2019.07.025.
43 OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin. Am J Hum Genet. 2009 Oct;85(4):465-81. doi: 10.1016/j.ajhg.2009.09.002.
44 The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet. 2007 Jul;39(7):875-81. doi: 10.1038/ng2039. Epub 2007 Jun 10.
45 Clinical nosologic and genetic aspects of Joubert and related syndromes.J Child Neurol. 1999 Oct;14(10):660-6; discussion 669-72. doi: 10.1177/088307389901401007.
46 A novel pathogenic variant in OFD1 results in X-linked Joubert syndrome with orofaciodigital features and pituitary aplasia.Am J Med Genet A. 2019 Jun;179(6):1010-1014. doi: 10.1002/ajmg.a.61018. Epub 2019 Mar 20.
47 A novel PDE6D mutation in a patient with Joubert syndrome type 22 (JBTS22).Eur J Med Genet. 2019 Nov;62(11):103576. doi: 10.1016/j.ejmg.2018.11.010. Epub 2018 Nov 10.
48 Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.Kidney Int. 2016 Feb;89(2):468-475. doi: 10.1038/ki.2015.317.
49 A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies.Nat Genet. 2009 Jun;41(6):739-45. doi: 10.1038/ng.366. Epub 2009 May 10.
50 Tectonic gene mutations in patients with Joubert syndrome.Eur J Hum Genet. 2015 May;23(5):616-20. doi: 10.1038/ejhg.2014.160. Epub 2014 Aug 13.
51 Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.Am J Med Genet A. 2017 Jul;173(7):1796-1812. doi: 10.1002/ajmg.a.38272. Epub 2017 May 12.
52 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.