JBTS21
MCID: JBR031
MIFTS: 42

Joubert Syndrome 21 (JBTS21)

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

Aliases & Classifications for Joubert Syndrome 21

MalaCards integrated aliases for Joubert Syndrome 21:

Name: Joubert Syndrome 21 57 12 72 29 6 15 70
Jbts21 57 12 72
Joubert Syndrome, Type 21 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
may result in early death
variable features
prenatal onset


HPO:

31
joubert syndrome 21:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity congenital onset


Classifications:



Summaries for Joubert Syndrome 21

OMIM® : 57 Joubert syndrome is an autosomal recessive congenital condition characterized by a unique brainstem and cerebellar malformation comprising cerebellar vermis hypoplasia and/or dysplasia, elongated superior cerebellar peduncles, and deepened interpeduncular fossa, which together are recognized as the 'molar tooth sign' on brain MRI. The most common clinical features include delayed psychomotor development, hypotonia, abnormal respiratory patterns in the neonatal period, oculomotor apraxia, and cerebellar ataxia. Additional features may include retinal degeneration, cystic kidney, liver fibrosis, and polydactyly. It is caused by ciliary defects and is part of a spectrum of disorders known as 'ciliopathies' (summary by Akizu et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300. (615636) (Updated 05-Apr-2021)

MalaCards based summary : Joubert Syndrome 21, also known as jbts21, is related to cerebellar malformation and oculomotor apraxia, and has symptoms including dyspnea, apnea and cerebellar ataxia. An important gene associated with Joubert Syndrome 21 is CSPP1 (Centrosome And Spindle Pole Associated Protein 1), and among its related pathways/superpathways are Regulation of PLK1 Activity at G2/M Transition and Organelle biogenesis and maintenance. Affiliated tissues include brain and liver, and related phenotypes are sensorineural hearing impairment and retinopathy

Disease Ontology : 12 A Joubert syndrome that has material basis in homozygous or compound heterozygous mutation in the CSPP1 gene on chromosome 8q13.

UniProtKB/Swiss-Prot : 72 Joubert syndrome 21: 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, renal disease, liver fibrosis, and polydactyly.

Related Diseases for Joubert Syndrome 21

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 Joubert Syndrome 36
Joubert Syndrome 37

Diseases related to Joubert Syndrome 21 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 cerebellar malformation 10.1 KATNIP CEP104
2 oculomotor apraxia 10.1 CSPP1 CEP104
3 apraxia 10.1 CSPP1 CEP104
4 congenital ptosis 10.1 CSPP1 ARFGEF1
5 nephronophthisis 12 10.0 CEP41 CEP164
6 spinocerebellar ataxia 11 10.0 CEP97 CEP164
7 orofaciodigital syndrome i 9.9 CEP97 CEP164
8 joubert syndrome 15 9.8 KIF7 CEP41
9 senior-loken syndrome 1 9.8 CEP97 CEP164 CEP104
10 coach syndrome 1 9.7 KIF7 CSPP1
11 joubert syndrome 3 9.7 KIF7 CEP41
12 ciliopathy 9.7 KIF7 KATNIP CEP41
13 acrocallosal syndrome 9.6 KIF7 KATNIP
14 short-rib thoracic dysplasia 1 with or without polydactyly 9.4 KIF7 KATNIP CSPP1 CEP41 CEP104
15 meckel syndrome, type 1 9.2 KIF7 CSPP1 CEP97 CEP41 CEP164
16 nephronophthisis 9.2 KIF7 CSPP1 CEP97 CEP41 CEP164
17 joubert syndrome 26 9.1 KIF7 KATNIP CSPP1 CEP97 CEP41 CEP104
18 asphyxiating thoracic dystrophy 9.1 KIF7 CSPP1 CEP41 CEP164 CEP104 ARFGEF1
19 joubert syndrome 25 9.0 KIF7 KATNIP CSPP1 CKAP5 CEP97 CEP104
20 fundus dystrophy 9.0 KIF7 KATNIP CSPP1 CEP97 CEP41 CEP164
21 joubert syndrome 1 8.2 SNTN KIF7 KATNIP CSPP1 CKAP5 CEP97

Graphical network of the top 20 diseases related to Joubert Syndrome 21:



Diseases related to Joubert Syndrome 21

Symptoms & Phenotypes for Joubert Syndrome 21

Human phenotypes related to Joubert Syndrome 21:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
2 retinopathy 31 occasional (7.5%) HP:0000488
3 anophthalmia 31 occasional (7.5%) HP:0000528
4 pulmonary hypoplasia 31 occasional (7.5%) HP:0002089
5 occipital encephalocele 31 occasional (7.5%) HP:0002085
6 renal cyst 31 occasional (7.5%) HP:0000107
7 bell-shaped thorax 31 occasional (7.5%) HP:0001591
8 single naris 31 occasional (7.5%) HP:0009932
9 hyperechogenic kidneys 31 occasional (7.5%) HP:0004719
10 intellectual disability 31 HP:0001249
11 ptosis 31 HP:0000508
12 ataxia 31 HP:0001251
13 global developmental delay 31 HP:0001263
14 strabismus 31 HP:0000486
15 dyspnea 31 HP:0002094
16 apnea 31 HP:0002104
17 hypoplasia of the corpus callosum 31 HP:0002079
18 oculomotor apraxia 31 HP:0000657
19 generalized hypotonia 31 HP:0001290
20 hypoplasia of the brainstem 31 HP:0002365
21 elongated superior cerebellar peduncle 31 HP:0011933
22 posterior fossa cyst 31 HP:0007291

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
strabismus
oculomotor apraxia
retinopathy (in some patients)
fused eyes (1 family)
more
Neurologic Central Nervous System:
hypoplasia of the brainstem
posterior fossa cyst
cerebellar ataxia
hypotonia
mental retardation
more
Head And Neck Ears:
sensorineural hearing loss (2 patients)

Chest External Features:
bell-shaped chest (in some patients)

Abdomen Liver:
liver fibrosis (in some patients)

Respiratory:
dyspnea
apnea
abnormal breathing pattern

Respiratory Lung:
pulmonary hypoplasia (in some patients)

Head And Neck Nose:
single nostril (1 family)

Chest Ribs Sternum Clavicles And Scapulae:
short, horizontal ribs (in some patients)

Genitourinary Kidneys:
hyperechogenic kidneys (in some patients)
cystic kidneys (in some patients)

Clinical features from OMIM®:

615636 (Updated 05-Apr-2021)

UMLS symptoms related to Joubert Syndrome 21:


dyspnea; apnea; cerebellar ataxia

GenomeRNAi Phenotypes related to Joubert Syndrome 21 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00240-S-1 9.7 ARFGEF1 CEP41 CKAP5 PLEKHG6
2 Decreased viability GR00249-S 9.7 CKAP5
3 Decreased viability GR00381-A-1 9.7 ARFGEF1
4 Decreased viability GR00386-A-1 9.7 CEP41 CKAP5 PLEKHG6
5 Decreased viability GR00402-S-2 9.7 ARFGEF1 CKAP5
6 Acentrosomal spindle poles GR00222-A-2 9.16 CEP164 CKAP5
7 Multipolar spindles GR00222-A-1 8.62 CEP164 CKAP5

Drugs & Therapeutics for Joubert Syndrome 21

Search Clinical Trials , NIH Clinical Center for Joubert Syndrome 21

Genetic Tests for Joubert Syndrome 21

Genetic tests related to Joubert Syndrome 21:

# Genetic test Affiliating Genes
1 Joubert Syndrome 21 29 CSPP1

Anatomical Context for Joubert Syndrome 21

MalaCards organs/tissues related to Joubert Syndrome 21:

40
Brain, Liver

Publications for Joubert Syndrome 21

Articles related to Joubert Syndrome 21:

# Title Authors PMID Year
1
Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. 6 57
24360808 2014
2
Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans. 6 57
24360803 2014
3
Mutations in CSPP1 lead to classical Joubert syndrome. 6 57
24360807 2014
4
Characterizing the morbid genome of ciliopathies. 6
27894351 2016
5
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. 6
26092869 2015

Variations for Joubert Syndrome 21

ClinVar genetic disease variations for Joubert Syndrome 21:

6 (show top 50) (show all 219)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CSPP1 NM_024790.6(CSPP1):c.2320C>T (p.Arg774Ter) SNV Pathogenic 100666 rs587777138 GRCh37: 8:68070775-68070775
GRCh38: 8:67158540-67158540
2 CSPP1 NM_024790.6(CSPP1):c.2280del (p.Glu761fs) Deletion Pathogenic 100668 rs587777140 GRCh37: 8:68070735-68070735
GRCh38: 8:67158500-67158500
3 ARFGEF1 , CSPP1 NM_024790.6(CSPP1):c.3212dup (p.Tyr1071Ter) Duplication Pathogenic 100669 rs587777141 GRCh37: 8:68102890-68102891
GRCh38: 8:67190655-67190656
4 CSPP1 NM_024790.6(CSPP1):c.2953+1G>A SNV Pathogenic 100670 rs587777142 GRCh37: 8:68084791-68084791
GRCh38: 8:67172556-67172556
5 CSPP1 NM_024790.6(CSPP1):c.2527_2528del (p.Met843fs) Deletion Pathogenic 100671 rs587777143 GRCh37: 8:68074049-68074050
GRCh38: 8:67161814-67161815
6 CSPP1 NM_024790.6(CSPP1):c.658C>T (p.Arg220Ter) SNV Pathogenic 100672 rs375113643 GRCh37: 8:68007675-68007675
GRCh38: 8:67095440-67095440
7 CSPP1 NM_024790.6(CSPP1):c.652C>T (p.Gln218Ter) SNV Pathogenic 100675 rs587777146 GRCh37: 8:68007669-68007669
GRCh38: 8:67095434-67095434
8 CSPP1 NM_024790.6(CSPP1):c.2773C>T (p.Arg925Ter) SNV Pathogenic 100676 rs537456518 GRCh37: 8:68076703-68076703
GRCh38: 8:67164468-67164468
9 CSPP1 NM_024790.6(CSPP1):c.457del (p.Arg153fs) Deletion Pathogenic 217644 rs863225192 GRCh37: 8:68005823-68005823
GRCh38: 8:67093588-67093588
10 ARFGEF1 , CSPP1 NM_024790.6(CSPP1):c.3205+1G>A SNV Pathogenic 217645 rs773954226 GRCh37: 8:68092162-68092162
GRCh38: 8:67179927-67179927
11 CSPP1 NM_024790.6(CSPP1):c.950+1G>C SNV Pathogenic 217649 rs863225194 GRCh37: 8:68007968-68007968
GRCh38: 8:67095733-67095733
12 CSPP1 NM_001291339.1(CSPP1):c.1398_1401AGAA[2] (p.Lys469fs) Microsatellite Pathogenic 217650 rs761382780 GRCh37: 8:68071282-68071285
GRCh38: 8:67159047-67159050
13 CSPP1 NM_024790.6(CSPP1):c.2708del (p.Asn903fs) Deletion Pathogenic 217642 rs863225190 GRCh37: 8:68076631-68076631
GRCh38: 8:67164396-67164396
14 CSPP1 NM_001291339.1(CSPP1):c.1406_1412AGAAGAA[3] (p.Glu474fs) Microsatellite Pathogenic 217643 rs863225191 GRCh37: 8:68071284-68071285
GRCh38: 8:67159049-67159050
15 CSPP1 NM_024790.6(CSPP1):c.1682+1G>T SNV Pathogenic 217647 rs863225193 GRCh37: 8:68031057-68031057
GRCh38: 8:67118822-67118822
16 CSPP1 NM_001291339.1(CSPP1):c.1406_1412AGAAGAA[1] (p.Glu472fs) Microsatellite Pathogenic 217651 rs863225191 GRCh37: 8:68071285-68071291
GRCh38: 8:67159050-67159056
17 CSPP1 NM_024790.6(CSPP1):c.2260C>T (p.Arg754Ter) SNV Pathogenic 217648 rs771203308 GRCh37: 8:68070715-68070715
GRCh38: 8:67158480-67158480
18 CSPP1 NM_024790.6(CSPP1):c.2814-9_2953+11del Deletion Pathogenic 434846 rs1554614893 GRCh37: 8:68084639-68084798
GRCh38: 8:67172404-67172563
19 CSPP1 NM_024790.6(CSPP1):c.2512dup (p.Glu838fs) Duplication Pathogenic 541695 rs1554604482 GRCh37: 8:68071357-68071358
GRCh38: 8:67159122-67159123
20 CSPP1 NM_024790.6(CSPP1):c.2525del (p.His842fs) Deletion Pathogenic 573876 rs1563720581 GRCh37: 8:68074047-68074047
GRCh38: 8:67161812-67161812
21 CSPP1 NM_024790.6(CSPP1):c.167_168del (p.Lys56fs) Deletion Pathogenic 575640 rs766020802 GRCh37: 8:67986545-67986546
GRCh38: 8:67074310-67074311
22 CSPP1 NM_024790.6(CSPP1):c.2953+1G>T SNV Pathogenic 804338 rs587777142 GRCh37: 8:68084791-68084791
GRCh38: 8:67172556-67172556
23 CSPP1 NM_024790.6(CSPP1):c.2089G>T (p.Glu697Ter) SNV Pathogenic 843899 GRCh37: 8:68062146-68062146
GRCh38: 8:67149911-67149911
24 CSPP1 NM_024790.6(CSPP1):c.1961-2A>G SNV Pathogenic 853035 GRCh37: 8:68062016-68062016
GRCh38: 8:67149781-67149781
25 CSPP1 NM_024790.6(CSPP1):c.1534C>T (p.Arg512Ter) SNV Pathogenic 860634 GRCh37: 8:68030535-68030535
GRCh38: 8:67118300-67118300
26 CSPP1 NM_001382391.1(CSPP1):c.19G>T (p.Glu7Ter) SNV Pathogenic 937081 GRCh37: 8:67986506-67986506
GRCh38: 8:67074271-67074271
27 CSPP1 NM_001382391.1(CSPP1):c.940C>T (p.Arg314Ter) SNV Pathogenic 959219 GRCh37: 8:68015288-68015288
GRCh38: 8:67103053-67103053
28 CSPP1 NM_001291339.1(CSPP1):c.1209_1212del (p.Glu405fs) Deletion Pathogenic 100674 rs587777145 GRCh37: 8:68070698-68070701
GRCh38: 8:67158463-67158466
29 CSPP1 NM_024790.6(CSPP1):c.1132C>T (p.Arg378Ter) SNV Pathogenic 217646 rs374703898 GRCh37: 8:68024218-68024218
GRCh38: 8:67111983-67111983
30 CSPP1 NM_001291339.1(CSPP1):c.1325_1326GA[2] (p.Lys444fs) Microsatellite Pathogenic 850442 GRCh37: 8:68070814-68070815
GRCh38: 8:67158579-67158580
31 CSPP1 NM_001382391.1(CSPP1):c.1187G>A (p.Arg396Gln) SNV Pathogenic 949594 GRCh37: 8:68024300-68024300
GRCh38: 8:67112065-67112065
32 CSPP1 NM_024790.6(CSPP1):c.2244_2245del (p.Glu750fs) Deletion Pathogenic 100667 rs587777139 GRCh37: 8:68070698-68070699
GRCh38: 8:67158463-67158464
33 CSPP1 NM_001382391.1(CSPP1):c.2521_2524del (p.Ile841fs) Deletion Pathogenic 1031405 GRCh37: 8:68071352-68071355
GRCh38: 8:67159117-67159120
34 CSPP1 NM_024790.6(CSPP1):c.363_364del (p.His121fs) Deletion Pathogenic 100673 rs1554562278 GRCh37: 8:67998296-67998297
GRCh38: 8:67086061-67086062
35 CSPP1 NM_024790.6(CSPP1):c.2815A>T (p.Lys939Ter) SNV Pathogenic 581963 rs1380418532 GRCh37: 8:68084652-68084652
GRCh38: 8:67172417-67172417
36 CSPP1 NM_001382391.1(CSPP1):c.132dup (p.Lys45Ter) Duplication Pathogenic 1030873 GRCh37: 8:67988748-67988749
GRCh38: 8:67076513-67076514
37 ARFGEF1 , CSPP1 NM_001382391.1(CSPP1):c.3331-2A>G SNV Likely pathogenic 958134 GRCh37: 8:68105697-68105697
GRCh38: 8:67193462-67193462
38 CSPP1 NM_024790.6(CSPP1):c.2366_2367del Deletion Likely pathogenic 918073 GRCh37:
GRCh38:
39 CSPP1 NC_000008.11:g.(?_67149783)_(67177726_?)dup Duplication Likely pathogenic 833371 GRCh37: 8:68062018-68089961
GRCh38:
40 CSPP1 NM_024790.6(CSPP1):c.2205C>A (p.Tyr735Ter) SNV Likely pathogenic 434847 rs1402669959 GRCh37: 8:68066350-68066350
GRCh38: 8:67154115-67154115
41 ARFGEF1 , CSPP1 NM_024790.6(CSPP1):c.3281A>G (p.Glu1094Gly) SNV Conflicting interpretations of pathogenicity 510229 rs201629827 GRCh37: 8:68102960-68102960
GRCh38: 8:67190725-67190725
42 ARFGEF1 , CSPP1 NM_001382391.1(CSPP1):c.3292C>T (p.Arg1098Trp) SNV Uncertain significance 1030874 GRCh37: 8:68102956-68102956
GRCh38: 8:67190721-67190721
43 CSPP1 NM_001382391.1(CSPP1):c.959T>G (p.Met320Arg) SNV Uncertain significance 1031406 GRCh37: 8:68015307-68015307
GRCh38: 8:67103072-67103072
44 CSPP1 NM_001382391.1(CSPP1):c.2129G>T (p.Gly710Val) SNV Uncertain significance 1034854 GRCh37: 8:68066259-68066259
GRCh38: 8:67154024-67154024
45 ARFGEF1 , CSPP1 NM_001382391.1(CSPP1):c.3040C>A (p.Gln1014Lys) SNV Uncertain significance 1037109 GRCh37: 8:68087602-68087602
GRCh38: 8:67175367-67175367
46 CSPP1 NM_001382391.1(CSPP1):c.2114C>A (p.Ala705Glu) SNV Uncertain significance 1038166 GRCh37: 8:68062156-68062156
GRCh38: 8:67149921-67149921
47 ARFGEF1 , CSPP1 NM_001382391.1(CSPP1):c.3533_3536dup (p.Val1180fs) Duplication Uncertain significance 1039538 GRCh37: 8:68107679-68107680
GRCh38: 8:67195444-67195445
48 ARFGEF1 , CSPP1 NM_001382391.1(CSPP1):c.3587G>A (p.Arg1196His) SNV Uncertain significance 1042214 GRCh37: 8:68107734-68107734
GRCh38: 8:67195499-67195499
49 CSPP1 NM_001382391.1(CSPP1):c.1571A>T (p.Tyr524Phe) SNV Uncertain significance 1042230 GRCh37: 8:68030557-68030557
GRCh38: 8:67118322-67118322
50 CSPP1 NM_001382391.1(CSPP1):c.1568C>A (p.Ala523Glu) SNV Uncertain significance 1042417 GRCh37: 8:68030554-68030554
GRCh38: 8:67118319-67118319

Expression for Joubert Syndrome 21

Search GEO for disease gene expression data for Joubert Syndrome 21.

Pathways for Joubert Syndrome 21

GO Terms for Joubert Syndrome 21

Cellular components related to Joubert Syndrome 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.07 PLEKHG6 KIF7 KATNIP CSPP1 CKAP5 CEP97
2 cell projection GO:0042995 9.8 SNTN PLEKHG6 KIF7 KATNIP CEP41 CEP104
3 cilium GO:0005929 9.71 SNTN KIF7 CEP41 CEP104
4 microtubule organizing center GO:0005815 9.65 CSPP1 CKAP5 CEP97 CEP41 CEP104
5 spindle GO:0005819 9.63 PLEKHG6 CSPP1 CKAP5
6 centriole GO:0005814 9.61 CEP41 CEP164 CEP104
7 spindle pole GO:0000922 9.46 PLEKHG6 CSPP1 CKAP5 CEP104
8 centrosome GO:0005813 9.43 PLEKHG6 CSPP1 CKAP5 CEP97 CEP41 CEP164
9 cytoskeleton GO:0005856 9.28 PLEKHG6 KIF7 KATNIP CSPP1 CKAP5 CEP97

Biological processes related to Joubert Syndrome 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection organization GO:0030030 9.43 CEP97 CEP41 CEP164
2 G2/M transition of mitotic cell cycle GO:0000086 9.33 CKAP5 CEP41 CEP164
3 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.13 CKAP5 CEP41 CEP164
4 ciliary basal body-plasma membrane docking GO:0097711 8.92 CKAP5 CEP97 CEP41 CEP164

Sources for Joubert Syndrome 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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