JBTS2
MCID: JBR004
MIFTS: 39

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 58 12 54 76 30 13 6 45 15 74
Cerebellooculorenal Syndrome 2 58 12 54 76
Jbts2 58 12 54 76
Cors2 58 12 54 76
Cerebellooculorenal Syndrome 2; Cors2 58
Cerebello-Oculo-Renal Syndrome 2 76
Joubert Syndrome, Type 2 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
genetic heterogeneity


HPO:

33
joubert syndrome 2:
Onset and clinical course phenotypic variability
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Joubert Syndrome 2

OMIM : 58 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 : 76 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

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:

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

Symptoms via clinical synopsis from OMIM:

58
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 30 TMEM216

Anatomical Context for Joubert Syndrome 2

MalaCards organs/tissues related to Joubert Syndrome 2:

42
Brain, Eye

Publications for Joubert Syndrome 2

Articles related to Joubert Syndrome 2:

# Title Authors Year
1
Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. ( 20036350 )
2010

Variations for Joubert Syndrome 2

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

76
# 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

ClinVar genetic disease variations for Joubert Syndrome 2:

6 (show all 50)
# Gene Variation Type Significance SNP ID Assembly Location
1 TMEM216 NM_001173990.2(TMEM216): c.216T> C (p.Ile72=) single nucleotide variant Likely pathogenic rs541666319 GRCh38 Chromosome 11, 61393963: 61393963
2 TMEM216 NM_001173990.2(TMEM216): c.216T> C (p.Ile72=) single nucleotide variant Likely pathogenic rs541666319 GRCh37 Chromosome 11, 61161435: 61161435
3 TMEM216 NM_001173990.2(TMEM216): c.217C> T (p.Arg73Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs779526456 GRCh38 Chromosome 11, 61393964: 61393964
4 TMEM216 NM_001173990.2(TMEM216): c.217C> T (p.Arg73Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs779526456 GRCh37 Chromosome 11, 61161436: 61161436
5 TMEM216 NM_001173990.2(TMEM216): c.398T> G (p.Leu133Ter) single nucleotide variant Pathogenic/Likely pathogenic rs755459875 GRCh38 Chromosome 11, 61397942: 61397942
6 TMEM216 NM_001173990.2(TMEM216): c.398T> G (p.Leu133Ter) single nucleotide variant Pathogenic/Likely pathogenic rs755459875 GRCh37 Chromosome 11, 61165414: 61165414
7 TMEM216 NM_001173990.2(TMEM216): c.218G> T (p.Arg73Leu) single nucleotide variant Pathogenic rs201108965 GRCh37 Chromosome 11, 61161437: 61161437
8 TMEM216 NM_001173990.2(TMEM216): c.218G> T (p.Arg73Leu) single nucleotide variant Pathogenic rs201108965 GRCh38 Chromosome 11, 61393965: 61393965
9 TMEM216 NM_001173990.2(TMEM216): c.218G> A (p.Arg73His) single nucleotide variant Pathogenic rs201108965 GRCh37 Chromosome 11, 61161437: 61161437
10 TMEM216 NM_001173990.2(TMEM216): c.218G> A (p.Arg73His) single nucleotide variant Pathogenic rs201108965 GRCh38 Chromosome 11, 61393965: 61393965
11 TMEM216 NM_001173990.2(TMEM216): c.253C> T (p.Arg85Ter) single nucleotide variant Pathogenic/Likely pathogenic rs11230683 GRCh37 Chromosome 11, 61165269: 61165269
12 TMEM216 NM_001173990.2(TMEM216): c.253C> T (p.Arg85Ter) single nucleotide variant Pathogenic/Likely pathogenic rs11230683 GRCh38 Chromosome 11, 61397797: 61397797
13 TMEM216 NM_001173990.2(TMEM216): c.34+2T> C single nucleotide variant Likely pathogenic rs1057517498 GRCh37 Chromosome 11, 61160139: 61160139
14 TMEM216 NM_001173990.2(TMEM216): c.34+2T> C single nucleotide variant Likely pathogenic rs1057517498 GRCh38 Chromosome 11, 61392667: 61392667
15 TMEM216 NM_001173990.2(TMEM216): c.35-2A> G single nucleotide variant Likely pathogenic rs1057517528 GRCh38 Chromosome 11, 61393229: 61393229
16 TMEM216 NM_001173990.2(TMEM216): c.35-2A> G single nucleotide variant Likely pathogenic rs1057517528 GRCh37 Chromosome 11, 61160701: 61160701
17 TMEM216 NM_001173990.2(TMEM216): c.222delG (p.Phe76Leufs) deletion Likely pathogenic rs1057517512 GRCh37 Chromosome 11, 61161441: 61161441
18 TMEM216 NM_001173990.2(TMEM216): c.222delG (p.Phe76Leufs) deletion Likely pathogenic rs1057517512 GRCh38 Chromosome 11, 61393969: 61393969
19 TMEM216 NM_001173990.2(TMEM216): c.228delT (p.Phe76Leufs) deletion Likely pathogenic rs767384710 GRCh37 Chromosome 11, 61161447: 61161447
20 TMEM216 NM_001173990.2(TMEM216): c.228delT (p.Phe76Leufs) deletion Likely pathogenic rs767384710 GRCh38 Chromosome 11, 61393975: 61393975
21 TMEM216 NM_001173990.2(TMEM216): c.228dupT (p.Gly77Trpfs) duplication Likely pathogenic rs767384710 GRCh38 Chromosome 11, 61393975: 61393975
22 TMEM216 NM_001173990.2(TMEM216): c.228dupT (p.Gly77Trpfs) duplication Likely pathogenic rs767384710 GRCh37 Chromosome 11, 61161447: 61161447
23 TMEM216 NM_001173990.2(TMEM216): c.1A> G (p.Met1Val) single nucleotide variant Uncertain significance rs1287246452 GRCh37 Chromosome 11, 61160104: 61160104
24 TMEM216 NM_001173990.2(TMEM216): c.1A> G (p.Met1Val) single nucleotide variant Uncertain significance rs1287246452 GRCh38 Chromosome 11, 61392632: 61392632
25 TMEM216 NM_001173990.2(TMEM216): c.432-10delGinsAC indel Uncertain significance rs1554973021 GRCh37 Chromosome 11, 61165731: 61165732
26 TMEM216 NM_001173990.2(TMEM216): c.432-10delGinsAC indel Uncertain significance rs1554973021 GRCh38 Chromosome 11, 61398260: 61398260
27 TMEM216 NM_001173990.2(TMEM216): c.316_317insTA (p.Tyr106Leufs) insertion Likely pathogenic rs1554972958 GRCh37 Chromosome 11, 61165332: 61165332
28 TMEM216 NM_001173990.2(TMEM216): c.316_317insTA (p.Tyr106Leufs) insertion Likely pathogenic rs1554972958 GRCh38 Chromosome 11, 61397860: 61397861
29 TMEM216 NM_001173990.2(TMEM216): c.336C> A (p.Tyr112Ter) single nucleotide variant Likely pathogenic rs147267631 GRCh37 Chromosome 11, 61165352: 61165352
30 TMEM216 NM_001173990.2(TMEM216): c.336C> A (p.Tyr112Ter) single nucleotide variant Likely pathogenic rs147267631 GRCh38 Chromosome 11, 61397880: 61397880
31 TMEM216 NM_001173990.2(TMEM216): c.2T> A (p.Met1Lys) single nucleotide variant Uncertain significance rs1554972406 GRCh37 Chromosome 11, 61160105: 61160105
32 TMEM216 NM_001173990.2(TMEM216): c.2T> A (p.Met1Lys) single nucleotide variant Uncertain significance rs1554972406 GRCh38 Chromosome 11, 61392633: 61392633
33 TMEM216 NM_001173990.2(TMEM216): c.34+18_34+21delTGTG deletion Likely benign rs940443692 GRCh37 Chromosome 11, 61160151: 61160155
34 TMEM216 NM_001173990.2(TMEM216): c.34+18_34+21delTGTG deletion Likely benign rs940443692 GRCh38 Chromosome 11, 61392683: 61392686
35 TMEM216 NM_001173990.2(TMEM216): c.137-1G> A single nucleotide variant Likely pathogenic rs1554972547 GRCh37 Chromosome 11, 61161355: 61161355
36 TMEM216 NM_001173990.2(TMEM216): c.137-1G> A single nucleotide variant Likely pathogenic rs1554972547 GRCh38 Chromosome 11, 61393883: 61393883
37 TMEM216 NM_001173990.2(TMEM216): c.230-9dup duplication Uncertain significance rs1554972934 GRCh37 Chromosome 11, 61165236: 61165236
38 TMEM216 NM_001173990.2(TMEM216): c.230-9dup duplication Uncertain significance rs1554972934 GRCh38 Chromosome 11, 61397765: 61397765
39 TMEM216 NM_001173990.2(TMEM216): c.432-10_432-8delGTAinsAGTG indel Uncertain significance rs1554973024 GRCh37 Chromosome 11, 61165731: 61165734
40 TMEM216 NM_001173990.2(TMEM216): c.432-10_432-8delGTAinsAGTG indel Uncertain significance rs1554973024 GRCh38 Chromosome 11, 61398260: 61398262
41 TMEM216 NM_001173990.2(TMEM216): c.432-10delGinsAA indel Uncertain significance rs1554973021 GRCh37 Chromosome 11, 61165731: 61165732
42 TMEM216 NM_001173990.2(TMEM216): c.432-10delGinsAA indel Uncertain significance rs1554973021 GRCh38 Chromosome 11, 61398260: 61398260
43 TMEM216 NM_001173990.2(TMEM216): c.-9_11del20 deletion Uncertain significance rs1554972400 GRCh37 Chromosome 11, 61160093: 61160113
44 TMEM216 NM_001173990.2(TMEM216): c.-9_11del20 deletion Uncertain significance rs1554972400 GRCh38 Chromosome 11, 61392623: 61392642
45 TMEM216 NM_001173990.2(TMEM216): c.2T> C (p.Met1Thr) single nucleotide variant Uncertain significance rs1554972406 GRCh37 Chromosome 11, 61160105: 61160105
46 TMEM216 NM_001173990.2(TMEM216): c.2T> C (p.Met1Thr) single nucleotide variant Uncertain significance rs1554972406 GRCh38 Chromosome 11, 61392633: 61392633
47 TMEM216 NM_001173990.2(TMEM216): c.164_168del5 (p.Asn55Serfs) deletion Likely pathogenic rs1554972556 GRCh37 Chromosome 11, 61161379: 61161384
48 TMEM216 NM_001173990.2(TMEM216): c.164_168del5 (p.Asn55Serfs) deletion Likely pathogenic rs1554972556 GRCh38 Chromosome 11, 61393911: 61393915
49 TMEM216 NM_001173990.2(TMEM216): c.338dup (p.Leu114Thrfs) duplication Uncertain significance rs1554972964 GRCh37 Chromosome 11, 61165353: 61165353
50 TMEM216 NM_001173990.2(TMEM216): c.338dup (p.Leu114Thrfs) duplication Uncertain significance rs1554972964 GRCh38 Chromosome 11, 61397882: 61397882

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 NPHP1 TMEM216 TMEM67
2 11.86 APPL1 GLI3 RHOA
3 10.61 GLI3 RHOA

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 NPHP1 RHOA TMEM216 TMEM67
2 cell projection GO:0042995 9.35 GLI3 NPHP1 RHOA TMEM216 TMEM67
3 ciliary transition zone GO:0035869 9.26 TMEM216 TMEM67
4 MKS complex GO:0036038 9.16 TMEM216 TMEM67
5 cilium GO:0005929 8.92 GLI3 NPHP1 TMEM216 TMEM67

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 NPHP1 TMEM216 TMEM67
2 negative regulation of neuron differentiation GO:0045665 9.32 GLI3 RHOA
3 positive regulation of alpha-beta T cell differentiation GO:0046638 9.16 GLI3 RHOA
4 ciliary basal body-plasma membrane docking GO:0097711 9.13 NPHP1 TMEM216 TMEM67
5 forebrain radial glial cell differentiation GO:0021861 8.62 GLI3 RHOA

Sources for Joubert Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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