JBTS2
MCID: JBR004
MIFTS: 40

Joubert Syndrome 2 (JBTS2)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Joubert Syndrome 2

MalaCards integrated aliases for Joubert Syndrome 2:

Name: Joubert Syndrome 2 57 12 53 74 29 13 6 44 15 72
Cerebellooculorenal Syndrome 2 57 12 53 74
Jbts2 57 12 53 74
Cors2 57 12 53 74
Cerebellooculorenal Syndrome 2; Cors2 57
Cerebello-Oculo-Renal Syndrome 2 74
Joubert Syndrome, Type 2 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
genetic heterogeneity


HPO:

32
joubert syndrome 2:
Inheritance autosomal recessive inheritance heterogeneous


Classifications:



External Ids:

Disease Ontology 12 DOID:0110988
MedGen 42 C1842577
UMLS 72 C1842577

Summaries for Joubert Syndrome 2

OMIM : 57 Joubert syndrome is a genetically heterogeneous autosomal recessive disorder characterized by a specific hindbrain malformation, which is referred to as the 'molar tooth sign' (MTS) on brain MRI, hypotonia, developmental delay, oculomotor apraxia, and breathing abnormalities. The complex brainstem malformation consists of cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (Maria et al., 1997). Additional features sometimes associated with Joubert syndrome include retinal anomalies, polydactyly, hepatic fibrosis, and renal disease. These related disorders are often referred to as 'cerebellooculorenal syndromes' (CORSs) (Chance et al., 1999; Satran et al., 1999). (608091)

MalaCards based summary : Joubert Syndrome 2, also known as cerebellooculorenal syndrome 2, is related to joubert syndrome 1 and joubert syndrome 16, and has symptoms including ataxia An important gene associated with Joubert Syndrome 2 is TMEM216 (Transmembrane Protein 216), and among its related pathways/superpathways are Organelle biogenesis and maintenance and Pathways in cancer. Affiliated tissues include brain and eye, and related phenotypes are macrocephaly and hypertelorism

Disease Ontology : 12 A Joubert syndrome characterized by molar tooth sign on brain MRI, hypotonia, developmental delay, oculomotor apraxia, and breathing abnormalities that has material basis in mutation in the TMEM216 gene on chromosome 11q12.2.

UniProtKB/Swiss-Prot : 74 Joubert syndrome 2: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease.

Related Diseases for Joubert Syndrome 2

Diseases in the Joubert Syndrome 1 family:

Joubert Syndrome 10 Joubert Syndrome 2
Joubert Syndrome 3 Joubert Syndrome 4
Joubert Syndrome 5 Joubert Syndrome 6
Joubert Syndrome 7 Joubert Syndrome 9
Joubert Syndrome 8 Joubert Syndrome 13
Joubert Syndrome 14 Joubert Syndrome 15
Joubert Syndrome 16 Joubert Syndrome 17
Joubert Syndrome 18 Joubert Syndrome 20
Joubert Syndrome 21 Joubert Syndrome 22
Joubert Syndrome 23 Joubert Syndrome 24
Joubert Syndrome 25 Joubert Syndrome 26
Joubert Syndrome 27 Joubert Syndrome 28
Joubert Syndrome 30 Joubert Syndrome 32
Joubert Syndrome 31 Joubert Syndrome 33
Joubert Syndrome 35

Diseases related to Joubert Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 joubert syndrome 1 28.2 TMEM67 TMEM216 NPHP1 C1QTNF3 APPL1
2 joubert syndrome 16 11.3
3 meckel syndrome, type 2 10.2 TMEM67 TMEM216
4 joubert syndrome 6 10.2 TMEM67 NPHP1
5 nephronophthisis 19 10.2 TMEM67 NPHP1
6 joubert syndrome 3 10.1 NPHP1 APPL1
7 meckel syndrome, type 3 10.1 TMEM67 NPHP1
8 nephronophthisis 11 10.1 TMEM67 NPHP1
9 senior-loken syndrome 1 9.9 TMEM67 TMEM216 NPHP1
10 cogan syndrome 9.9 NPHP1 APPL1
11 meckel syndrome, type 1 9.9 TMEM67 TMEM216 NPHP1
12 meckel syndrome, type 6 9.9 TMEM67 NPHP1
13 cerebellar hypoplasia 9.9
14 ataxia and polyneuropathy, adult-onset 9.9
15 apraxia 9.9
16 pathologic nystagmus 9.9
17 joubert syndrome with oculorenal anomalies 9.9
18 hypotonia 9.9
19 oculomotor apraxia 9.9
20 nephronophthisis 9.8 TMEM67 TMEM216 NPHP1
21 cystic kidney disease 9.7 TMEM67 NPHP1

Graphical network of the top 20 diseases related to Joubert Syndrome 2:



Diseases related to Joubert Syndrome 2

Symptoms & Phenotypes for Joubert Syndrome 2

Human phenotypes related to Joubert Syndrome 2:

32 (show all 44)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 32 HP:0000256
2 hypertelorism 32 HP:0000316
3 low-set ears 32 HP:0000369
4 frontal bossing 32 HP:0002007
5 high palate 32 HP:0000218
6 hydrocephalus 32 HP:0000238
7 nystagmus 32 HP:0000639
8 intellectual disability 32 HP:0001249
9 ataxia 32 HP:0001251
10 muscular hypotonia 32 HP:0001252
11 failure to thrive 32 HP:0001508
12 global developmental delay 32 HP:0001263
13 depressed nasal bridge 32 HP:0005280
14 visual impairment 32 HP:0000505
15 abnormal renal physiology 32 HP:0012211
16 dolichocephaly 32 HP:0000268
17 generalized hypotonia 32 HP:0001290
18 abnormality of the foot 32 HP:0001760
19 chorioretinal coloboma 32 HP:0000567
20 microphthalmia 32 HP:0000568
21 optic nerve coloboma 32 HP:0000588
22 nephronophthisis 32 HP:0000090
23 postaxial hand polydactyly 32 HP:0001162
24 encephalocele 32 HP:0002084
25 oculomotor apraxia 32 HP:0000657
26 dysgenesis of the cerebellar vermis 32 HP:0002195
27 renal cyst 32 HP:0000107
28 retinal dystrophy 32 HP:0000556
29 molar tooth sign on mri 32 HP:0002419
30 episodic tachypnea 32 HP:0002876
31 esotropia 32 HP:0000565
32 central apnea 32 HP:0002871
33 hypoplastic male external genitalia 32 HP:0000050
34 abnormality of ocular smooth pursuit 32 HP:0000617
35 impaired smooth pursuit 32 HP:0007772
36 abnormal corpus callosum morphology 32 HP:0001273
37 agenesis of cerebellar vermis 32 HP:0002335
38 hypoplasia of the brainstem 32 HP:0002365
39 elongated superior cerebellar peduncle 32 HP:0011933
40 brainstem dysplasia 32 HP:0002508
41 abnormal saccadic eye movements 32 HP:0000570
42 neonatal breathing dysregulation 32 HP:0002790
43 enlarged fossa interpeduncularis 32 HP:0100951
44 thickened superior cerebellar peduncle 32 HP:0002404

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly
dolichocephaly

Head And Neck Ears:
low-set ears

Neurologic Central Nervous System:
hydrocephalus
ataxia
encephalocele
hypoplasia of the brainstem
hypotonia
more
Head And Neck Nose:
depressed nasal bridge

Respiratory:
central apnea
neonatal breathing dysregulation
hyperpnea, episodic
tachypnea, episodic

Abdomen Gastrointestinal:
poor feeding in infancy
swallowing and chewing difficulties

Skeletal Hands:
polydactyly, postaxial

Head And Neck Eyes:
hypertelorism
nystagmus
visual impairment
chorioretinal coloboma
microphthalmia
more
Head And Neck Face:
frontal bossing

Growth Other:
failure to thrive

Genitourinary Kidneys:
nephronophthisis
renal cysts
impaired renal function (variable)

Head And Neck Mouth:
high-arched palate

Genitourinary External Genitalia Male:
hypoplastic genitalia

Skeletal Feet:
polydactyly, postaxial

Clinical features from OMIM:

608091

UMLS symptoms related to Joubert Syndrome 2:


ataxia

Drugs & Therapeutics for Joubert Syndrome 2

Search Clinical Trials , NIH Clinical Center for Joubert Syndrome 2

Cochrane evidence based reviews: joubert syndrome 2

Genetic Tests for Joubert Syndrome 2

Genetic tests related to Joubert Syndrome 2:

# Genetic test Affiliating Genes
1 Joubert Syndrome 2 29 TMEM216

Anatomical Context for Joubert Syndrome 2

MalaCards organs/tissues related to Joubert Syndrome 2:

41
Brain, Eye

Publications for Joubert Syndrome 2

Articles related to Joubert Syndrome 2:

(show all 13)
# Title Authors PMID Year
1
Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. 38 8 71
20512146 2010
2
Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. 38 8 71
20036350 2010
3
Distinguishing the four genetic causes of Jouberts syndrome-related disorders. 38 8
15786477 2005
4
Exome sequencing can improve diagnosis and alter patient management. 71
22700954 2012
5
Clinical utility gene card for: Joubert syndrome. 71
21448235 2011
6
Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. 71
21633164 2011
7
Linkage analysis in families with Joubert syndrome plus oculo-renal involvement identifies the CORS2 locus on chromosome 11p12-q13.3. 8
12917796 2003
8
Description, nomenclature, and mapping of a novel cerebello-renal syndrome with the molar tooth malformation. 8
12908130 2003
9
Joubert Syndrome 71
20301500 2003
10
Cerebello-oculo-renal syndromes including Arima, Senior-Löken and COACH syndromes: more than just variants of Joubert syndrome. 8
10508989 1999
11
Clinical nosologic and genetic aspects of Joubert and related syndromes. 8
10511339 1999
12
"Joubert syndrome" revisited: key ocular motor signs with magnetic resonance imaging correlation. 8
9373798 1997
13
C2cd3 is required for cilia formation and Hedgehog signaling in mouse. 38
19004860 2008

Variations for Joubert Syndrome 2

ClinVar genetic disease variations for Joubert Syndrome 2:

6 (show all 26)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TMEM216 NM_016499.5(TMEM216): c.35G> A (p.Arg12His) single nucleotide variant Pathogenic rs201108965 11:61161437-61161437 11:61393965-61393965
2 TMEM216 NM_016499.5(TMEM216): c.70C> T (p.Arg24Ter) single nucleotide variant Pathogenic/Likely pathogenic rs11230683 11:61165269-61165269 11:61397797-61397797
3 TMEM216 NM_016499.5(TMEM216): c.215T> G (p.Leu72Ter) single nucleotide variant Pathogenic/Likely pathogenic rs755459875 11:61165414-61165414 11:61397942-61397942
4 TMEM216 NM_016499.5(TMEM216): c.35G> T (p.Arg12Leu) single nucleotide variant Pathogenic/Likely pathogenic rs201108965 11:61161437-61161437 11:61393965-61393965
5 TMEM216 NM_001173990.3(TMEM216): c.164_168del (p.Asn55fs) deletion Likely pathogenic rs1554972556 11:61161379-61161384 11:61393911-61393915
6 TMEM216 NM_016499.5(TMEM216): c.33T> C (p.Ile11=) single nucleotide variant Likely pathogenic rs541666319 11:61161435-61161435 11:61393963-61393963
7 TMEM216 NM_016499.5(TMEM216): c.-47-1G> A single nucleotide variant Likely pathogenic rs1554972547 11:61161355-61161355 11:61393883-61393883
8 TMEM216 NM_016499.5(TMEM216): c.-162T> C single nucleotide variant Likely pathogenic rs1057517498 11:61160139-61160139 11:61392667-61392667
9 TMEM216 NM_016499.5(TMEM216): c.-149-2A> G single nucleotide variant Likely pathogenic rs1057517528 11:61160701-61160701 11:61393229-61393229
10 TMEM216 NM_016499.5(TMEM216): c.39del (p.Phe15fs) deletion Likely pathogenic rs1057517512 11:61161441-61161441 11:61393969-61393969
11 TMEM216 NM_016499.5(TMEM216): c.45del (p.Phe15fs) deletion Likely pathogenic rs767384710 11:61161447-61161447 11:61393975-61393975
12 TMEM216 NM_016499.5(TMEM216): c.45dup (p.Gly16fs) duplication Likely pathogenic rs767384710 11:61161447-61161447 11:61393975-61393975
13 TMEM216 NM_016499.5(TMEM216): c.133_134insTA (p.Tyr45fs) insertion Likely pathogenic rs1554972958 11:61165332-61165332 11:61397860-61397861
14 TMEM216 NM_016499.5(TMEM216): c.153C> A (p.Tyr51Ter) single nucleotide variant Likely pathogenic rs147267631 11:61165352-61165352 11:61397880-61397880
15 TMEM216 NM_016499.5(TMEM216): c.34C> T (p.Arg12Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs779526456 11:61161436-61161436 11:61393964-61393964
16 TMEM216 NM_016499.5(TMEM216): c.47-9dup duplication Uncertain significance rs1554972934 11:61165236-61165236 11:61397765-61397765
17 TMEM216 NM_016499.5(TMEM216): c.249-1_250delinsAGTG indel Uncertain significance rs1554973024 11:61165731-61165734 11:61398260-61398262
18 TMEM216 NM_016499.5(TMEM216): c.249-1delinsAA indel Uncertain significance rs1554973021 11:61165731-61165732 11:61398260-61398260
19 TMEM216 NM_001173990.3(TMEM216): c.-9_11del (p.Met1fs) deletion Uncertain significance rs1554972400 11:61160093-61160113 11:61392623-61392642
20 TMEM216 NM_001173990.3(TMEM216): c.2T> C (p.Met1Thr) single nucleotide variant Uncertain significance rs1554972406 11:61160105-61160105 11:61392633-61392633
21 TMEM216 NM_001173990.3(TMEM216): c.2T> A (p.Met1Lys) single nucleotide variant Uncertain significance rs1554972406 11:61160105-61160105 11:61392633-61392633
22 TMEM216 NM_001173990.3(TMEM216): c.1A> G (p.Met1Val) single nucleotide variant Uncertain significance rs1287246452 11:61160104-61160104 11:61392632-61392632
23 TMEM216 NM_016499.5(TMEM216): c.249-1delinsAC indel Uncertain significance rs1554973021 11:61165731-61165732 11:61398260-61398260
24 TMEM216 NM_016499.5(TMEM216): c.155dup (p.Leu53fs) duplication Uncertain significance rs1554972964 11:61165353-61165353 11:61397882-61397882
25 TMEM216 NM_001173990.3(TMEM216): c.140T> C (p.Val47Ala) single nucleotide variant Uncertain significance rs762918371 11:61161359-61161359 11:61393887-61393887
26 TMEM216 NM_001173990.2(TMEM216): c.34+18_34+21delTGTG deletion Likely benign rs940443692 11:61160151-61160155 11:61392683-61392686

UniProtKB/Swiss-Prot genetic disease variations for Joubert Syndrome 2:

74
# Symbol AA change Variation ID SNP ID
1 TMEM216 p.Arg73Leu VAR_063388 rs201108965
2 TMEM216 p.Arg73Cys VAR_064028 rs779526456
3 TMEM216 p.Arg73His VAR_064029 rs201108965
4 TMEM216 p.Leu89Phe VAR_068170 rs780098806

Expression for Joubert Syndrome 2

Search GEO for disease gene expression data for Joubert Syndrome 2.

Pathways for Joubert Syndrome 2

Pathways related to Joubert Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.06 TMEM67 TMEM216 NPHP1
2 11.86 RHOA GLI3 APPL1
3 10.61 RHOA GLI3

GO Terms for Joubert Syndrome 2

Cellular components related to Joubert Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.62 TMEM67 TMEM216 RHOA NPHP1
2 cell projection GO:0042995 9.35 TMEM67 TMEM216 RHOA NPHP1 GLI3
3 ciliary transition zone GO:0035869 9.26 TMEM67 TMEM216
4 MKS complex GO:0036038 9.16 TMEM67 TMEM216
5 cilium GO:0005929 8.92 TMEM67 TMEM216 NPHP1 GLI3

Biological processes related to Joubert Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection organization GO:0030030 9.43 TMEM67 TMEM216 NPHP1
2 negative regulation of neuron differentiation GO:0045665 9.32 RHOA GLI3
3 positive regulation of alpha-beta T cell differentiation GO:0046638 9.16 RHOA GLI3
4 ciliary basal body-plasma membrane docking GO:0097711 9.13 TMEM67 TMEM216 NPHP1
5 forebrain radial glial cell differentiation GO:0021861 8.62 RHOA GLI3

Sources for Joubert Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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