SCA15
MCID: SPN290
MIFTS: 43

Spinocerebellar Ataxia 15 (SCA15)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Spinocerebellar Ataxia 15

MalaCards integrated aliases for Spinocerebellar Ataxia 15:

Name: Spinocerebellar Ataxia 15 58 54 76 30 13 6 74
Sca15 58 25 54 76 56
Spinocerebellar Ataxia Type 15 12 25 54 15
Spinocerebellar Ataxia Type 16 12 76
Spinocerebellar Ataxia 16, Formerly; Sca16, Formerly 58
Spinocerebellar Ataxia 16, Formerly 58
Ataxia, Spinocerebellar, Type 15 41
Sca16, Formerly 58
Sca16 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
very slow progression
wide range of onset from childhood to adult (10 to 50 years)
most patients remain ambulatory
genetic heterogeneity, see sca1


HPO:

33
spinocerebellar ataxia 15:
Onset and clinical course adult onset slow progression juvenile onset
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance The penetrance is unknown. based on the even segregation ratio in older generations of the known sca15 pedigrees, penetrance is likely to be high or complete in these families. the late age of onset in some cases (≤72 years) may confound attempts to establish penetrance. apparently unaffected parents of three affected sibs were reported in one japanese pedigree, although detailed information on the parents was not available [obayashi et al 2012]. based on pedigree analysis, a parent who would have been predicted to have a pathogenic variant in one of the german families died young (age 31) and was asymptomatic at the time of death, potentially concealing disease development [synofzik et al 2011]...

Classifications:



External Ids:

Disease Ontology 12 DOID:0050965
OMIM 58 606658
MeSH 45 D020754
UMLS 74 C1847725

Summaries for Spinocerebellar Ataxia 15

OMIM : 58 SCA15 is an autosomal dominant, adult-onset, very slowly progressive form of cerebellar ataxia. Most patients also have disabling action and postural tremor, and some have pyramidal tract affection, dorsal column involvement, and gaze palsy. Brain imaging shows cerebellar atrophy mainly affecting the vermis (summary by Synofzik et al., 2011). Heterozygous mutation in the ITPR1 gene can also cause SCA29 (117360), which is distinguished by onset in infancy of delayed motor development followed by nonprogressive ataxia and mild cognitive impairment. Autosomal dominant 'pure' cerebellar ataxia, classified as ADCA type III by 3,4:Harding (1983, 1993), is a genetically heterogeneous disorder (see, e.g., 117210). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). (606658)

MalaCards based summary : Spinocerebellar Ataxia 15, also known as sca15, is related to autosomal dominant cerebellar ataxia and spinocerebellar ataxia 29, and has symptoms including gait ataxia, action tremor and scanning speech. An important gene associated with Spinocerebellar Ataxia 15 is ITPR1 (Inositol 1,4,5-Trisphosphate Receptor Type 1), and among its related pathways/superpathways is Neurophysiological process Glutamate regulation of Dopamine D1A receptor signaling. Affiliated tissues include eye, brain and testes, and related phenotypes are dysarthria and hyperreflexia

Disease Ontology : 12 An autosomal dominant cerebellar ataxia that is characterized by progressive ataxia, nystagmus, dysarthria and dysphagia, has material basis in mutation in the ITPR1 gene.

NIH Rare Diseases : 54 Spinocerebellar ataxia 15 (SCA15) is a neurological condition characterized by slowly progressive gait and limb ataxia, often in combination with eye movement abnormalities and  balance, speech and swallowing difficulties. The onset of symptoms typically occurs between ages 7 and 66 years. The ability to walk independently is often maintained for many years following onset of symptoms. SCA15 is caused by mutations in the ITPR1 gene. It is inherited in an autosomal dominant manner. Diagnosis is based on clinical history, physical examination, molecular genetic testing, and exclusion of other similar diseases. There is no effective treatment known to modify disease progression. Patients may benefit from occupational and physical therapy for gait dysfunction and speech therapy for dysarthria. 

UniProtKB/Swiss-Prot : 76 Spinocerebellar ataxia 15: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar ataxia (ADCA). It is very slow progressing form with a wide range of onset, ranging from childhood to adult. Most patients remain ambulatory.

GeneReviews: NBK1362

Related Diseases for Spinocerebellar Ataxia 15

Diseases in the Spinocerebellar Ataxia 2 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 6
Spinocerebellar Ataxia, Autosomal Recessive 2 Spinocerebellar Ataxia, Autosomal Recessive 3
Spinocerebellar Ataxia 4 Spinocerebellar Ataxia 5
Spinocerebellar Ataxia 10 Spinocerebellar Ataxia 12
Spinocerebellar Ataxia 11 Spinocerebellar Ataxia 13
Spinocerebellar Ataxia 14 Spinocerebellar Ataxia 15
Spinocerebellar Ataxia 17 Spinocerebellar Ataxia, Autosomal Recessive 4
Spinocerebellar Ataxia 19 Spinocerebellar Ataxia 21
Spinocerebellar Ataxia 18 Spinocerebellar Ataxia, Autosomal Recessive 6
Spinocerebellar Ataxia 20 Spinocerebellar Ataxia 25
Spinocerebellar Ataxia 8 Spinocerebellar Ataxia, Autosomal Recessive 7
Spinocerebellar Ataxia 26 Spinocerebellar Ataxia 27
Spinocerebellar Ataxia 23 Spinocerebellar Ataxia 28
Spinocerebellar Ataxia, Autosomal Recessive 8 Spinocerebellar Ataxia 9
Spinocerebellar Ataxia 30 Spinocerebellar Ataxia, Autosomal Recessive 10
Spinocerebellar Ataxia 35 Spinocerebellar Ataxia 32
Spinocerebellar Ataxia 36 Spinocerebellar Ataxia, Autosomal Recessive 11
Spinocerebellar Ataxia, Autosomal Recessive 12 Spinocerebellar Ataxia, Autosomal Recessive 13
Spinocerebellar Ataxia, Autosomal Recessive 14 Spinocerebellar Ataxia, Autosomal Recessive 15
Spinocerebellar Ataxia, Autosomal Recessive 16 Spinocerebellar Ataxia 37
Spinocerebellar Ataxia 38 Spinocerebellar Ataxia 40
Spinocerebellar Ataxia, Autosomal Recessive 17 Spinocerebellar Ataxia, Autosomal Recessive 18
Spinocerebellar Ataxia, Autosomal Recessive 20 Spinocerebellar Ataxia 41
Spinocerebellar Ataxia, Autosomal Recessive 21 Spinocerebellar Ataxia 42
Spinocerebellar Ataxia, Autosomal Recessive 22 Spinocerebellar Ataxia, Autosomal Recessive 23
Spinocerebellar Ataxia 43 Spinocerebellar Ataxia, Autosomal Recessive 24
Spinocerebellar Ataxia, Autosomal Recessive 25 Spinocerebellar Ataxia, Autosomal Recessive 26
Spinocerebellar Ataxia 44 Spinocerebellar Ataxia 45
Spinocerebellar Ataxia 46 Spinocerebellar Ataxia 47
Spinocerebellar Ataxia 48 Spinocerebellar Ataxia, Autosomal Recessive 27
Spinocerebellar Ataxia Type 19/22 Grid2-Related Spinocerebellar Ataxia
Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia 15 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 autosomal dominant cerebellar ataxia 29.7 KCNC3 SPTBN2
2 spinocerebellar ataxia 29 11.6
3 spinocerebellar ataxia, autosomal recessive 15 11.3
4 dystonia 10.1
5 myoclonus 10.1
6 ataxia and polyneuropathy, adult-onset 10.0
7 microcephaly with or without chorioretinopathy, lymphedema, or mental retardation 9.9 ITPR1 SPTBN2
8 spinocerebellar ataxia 28 9.9 KCNC3 PDYN
9 hereditary ataxia 9.7 KCNC3 SPTBN2
10 cerebral palsy, ataxic, autosomal recessive 9.7 ITPR1 KCNC3 SPTBN2
11 cerebellar disease 9.7 ITPR1 PDYN SPTBN2
12 autosomal recessive cerebellar ataxia 9.6 SPTBN2 STUB1
13 aceruloplasminemia 9.4 ITPR1 KCNC3 PDYN SPTBN2

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia 15:



Diseases related to Spinocerebellar Ataxia 15

Symptoms & Phenotypes for Spinocerebellar Ataxia 15

Human phenotypes related to Spinocerebellar Ataxia 15:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 dysarthria 33 HP:0001260
2 hyperreflexia 33 HP:0001347
3 gait ataxia 33 HP:0002066
4 limb ataxia 33 HP:0002070
5 truncal ataxia 33 HP:0002078
6 postural tremor 33 HP:0002174
7 cerebellar atrophy 33 HP:0001272
8 scanning speech 33 HP:0002168
9 gaze-evoked horizontal nystagmus 33 HP:0007979
10 impaired smooth pursuit 33 HP:0007772
11 dysmetric saccades 33 HP:0000641

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
dysarthria
hyperreflexia
gait ataxia
limb ataxia
truncal ataxia
more
Head And Neck Eyes:
impaired smooth pursuit
dysmetric saccades
nystagmus, horizontal, gaze-evoked

Clinical features from OMIM:

606658

UMLS symptoms related to Spinocerebellar Ataxia 15:


gait ataxia, action tremor, scanning speech, cerebellar ataxia, ataxia, truncal, static tremor

MGI Mouse Phenotypes related to Spinocerebellar Ataxia 15:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.63 ITPR1 KCNC3 PDYN SPTBN2 STUB1 SUMF1
2 growth/size/body region MP:0005378 9.43 ITPR1 KCNC3 PDYN SPTBN2 STUB1 SUMF1
3 nervous system MP:0003631 9.17 CNTN4 ITPR1 KCNC3 PDYN SPTBN2 STUB1

Drugs & Therapeutics for Spinocerebellar Ataxia 15

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Spinocerebellar Ataxia 15

Genetic Tests for Spinocerebellar Ataxia 15

Genetic tests related to Spinocerebellar Ataxia 15:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia 15 30 ITPR1

Anatomical Context for Spinocerebellar Ataxia 15

MalaCards organs/tissues related to Spinocerebellar Ataxia 15:

42
Eye, Brain, Testes, Spinal Cord, Cerebellum, Skin, Liver

Publications for Spinocerebellar Ataxia 15

Articles related to Spinocerebellar Ataxia 15:

(show all 13)
# Title Authors Year
1
Spinocerebellar ataxia 15: A phenotypic review and expansion. ( 27908616 )
2017
2
SCA15 due to large ITPR1 deletions in a cohort of 333 white families with dominant ataxia. ( 21555639 )
2011
3
Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family. ( 21689634 )
2011
4
An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description. ( 20669319 )
2010
5
Two Italian families with ITPR1 gene deletion presenting a broader phenotype of SCA15. ( 20082166 )
2010
6
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. ( 20050888 )
2010
7
"SCA16" is really SCA15. ( 18310270 )
2008
8
Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. ( 18579805 )
2008
9
Heterozygous deletion of ITPR1, but not SUMF1, in spinocerebellar ataxia type 16. ( 17932120 )
2008
10
Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. ( 17590087 )
2007
11
Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus. ( 14981189 )
2004
12
Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. ( 15623688 )
2004
13
Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant. ( 12828938 )
2003

Variations for Spinocerebellar Ataxia 15

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia 15:

76
# Symbol AA change Variation ID SNP ID
1 ITPR1 p.Pro1083Leu VAR_081167 rs121912425

ClinVar genetic disease variations for Spinocerebellar Ataxia 15:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 ITPR1 NC_000003.12 deletion Pathogenic GRCh38 Chromosome 3, 4480596: 4793915
2 ITPR1 NM_002222.5(ITPR1): c.3176C> T (p.Pro1059Leu) single nucleotide variant Pathogenic rs121912425 GRCh37 Chromosome 3, 4725156: 4725156
3 ITPR1 NM_002222.5(ITPR1): c.3176C> T (p.Pro1059Leu) single nucleotide variant Pathogenic rs121912425 GRCh38 Chromosome 3, 4683472: 4683472
4 ITPR1 NM_001168272.1(ITPR1): c.7739G> A (p.Gly2580Glu) single nucleotide variant Pathogenic rs869312685 GRCh37 Chromosome 3, 4856819: 4856819
5 ITPR1 NM_001168272.1(ITPR1): c.7739G> A (p.Gly2580Glu) single nucleotide variant Pathogenic rs869312685 GRCh38 Chromosome 3, 4815135: 4815135
6 ITPR1 NM_001168272.1(ITPR1): c.3619G> A (p.Ala1207Thr) single nucleotide variant Uncertain significance rs372881053 GRCh37 Chromosome 3, 4726852: 4726852
7 ITPR1 NM_001168272.1(ITPR1): c.3619G> A (p.Ala1207Thr) single nucleotide variant Uncertain significance rs372881053 GRCh38 Chromosome 3, 4685168: 4685168
8 ITPR1 NM_001168272.1(ITPR1): c.3206C> T (p.Pro1069Leu) single nucleotide variant Uncertain significance rs1467772045 GRCh37 Chromosome 3, 4725159: 4725159
9 ITPR1 NM_001168272.1(ITPR1): c.3206C> T (p.Pro1069Leu) single nucleotide variant Uncertain significance rs1467772045 GRCh38 Chromosome 3, 4683475: 4683475
10 ITPR1 NM_002222.5(ITPR1): c.7459G> A (p.Gly2487Arg) single nucleotide variant Uncertain significance rs1553757628 GRCh37 Chromosome 3, 4856193: 4856193
11 ITPR1 NM_002222.5(ITPR1): c.7459G> A (p.Gly2487Arg) single nucleotide variant Uncertain significance rs1553757628 GRCh38 Chromosome 3, 4814509: 4814509
12 ITPR1; ITPR1-DT; SETMAR; SUMF1 NC_000003.12: g.4092540_4624185del531646 deletion Pathogenic GRCh37 Chromosome 3, 4134224: 4665869
13 ITPR1; ITPR1-DT; SETMAR; SUMF1 NC_000003.12: g.4092540_4624185del531646 deletion Pathogenic GRCh38 Chromosome 3, 4092540: 4624185

Expression for Spinocerebellar Ataxia 15

Search GEO for disease gene expression data for Spinocerebellar Ataxia 15.

Pathways for Spinocerebellar Ataxia 15

Pathways related to Spinocerebellar Ataxia 15 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.58 ITPR1 PDYN

GO Terms for Spinocerebellar Ataxia 15

Cellular components related to Spinocerebellar Ataxia 15 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell cortex GO:0005938 8.96 KCNC3 SPTBN2
2 neuronal cell body GO:0043025 8.8 KCNC3 PDYN SPTBN2

Sources for Spinocerebellar Ataxia 15

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63 PubMed
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70 SNOMED-CT via HPO
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75 UMLS via Orphanet
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