SCA15
MCID: SPN290
MIFTS: 40

Spinocerebellar Ataxia 15 (SCA15)

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

Aliases & Classifications for Spinocerebellar Ataxia 15

MalaCards integrated aliases for Spinocerebellar Ataxia 15:

Name: Spinocerebellar Ataxia 15 56 52 73 13 71
Sca15 56 24 52 73 54
Spinocerebellar Ataxia Type 15 12 24 52 15
Spinocerebellar Ataxia Type 16 12 73 29 6
Spinocerebellar Ataxia Type 15/16 58 6
Spinocerebellar Ataxia 16, Formerly; Sca16, Formerly 56
Spinocerebellar Ataxia 16, Formerly 56
Ataxia, Spinocerebellar, Type 15 39
Sca16, Formerly 56
Sca15/16 58
Sca16 73

Characteristics:

Orphanet epidemiological data:

58
spinocerebellar ataxia type 15/16
Inheritance: Autosomal dominant;

OMIM:

56
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:

31
spinocerebellar ataxia 15:
Inheritance autosomal dominant inheritance
Onset and clinical course juvenile onset adult onset slow progression


GeneReviews:

24
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:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0050965
OMIM 56 606658
OMIM Phenotypic Series 56 PS164400
MeSH 43 D020754
ICD10 via Orphanet 33 G11.2
Orphanet 58 ORPHA98769
UMLS 71 C1847725

Summaries for Spinocerebellar Ataxia 15

OMIM : 56 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 spinocerebellar ataxia 29 and hereditary ataxia, and has symptoms including gait ataxia, scanning speech and action tremor. 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 Spinocerebellar ataxia. Affiliated tissues include eye, brain and cerebellum, and related phenotypes are hyperreflexia and gait ataxia

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 : 52 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 : 73 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 6 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 2
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, Autosomal Recessive 28 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 42)
# Related Disease Score Top Affiliating Genes
1 spinocerebellar ataxia 29 32.8 ITPR1 AFG3L2
2 hereditary ataxia 28.3 TTBK2 SPTBN2 SACS KCNC3 ITPR1 AFG3L2
3 autosomal dominant cerebellar ataxia 28.1 TTBK2 SPTBN2 SACS KCNC3 ITPR1 BLOC1S1
4 spinocerebellar ataxia, autosomal recessive 15 11.4
5 tremor 10.4
6 dentatorubral-pallidoluysian atrophy 10.3
7 ataxia and polyneuropathy, adult-onset 10.2
8 cerebellar degeneration 10.2
9 cerebellar ataxia type 9 10.2 SPTBN2 KCNC3
10 cerebellar hypoplasia 10.2
11 cerebellar ataxia type 41 10.1 KCNC3 AFG3L2
12 episodic ataxia, type 6 10.1 SPTBN2 KCNC3
13 spinocerebellar ataxia 5 10.1 SPTBN2 ITPR1
14 spinocerebellar ataxia 25 10.1 TTBK2 CNTN4
15 gordon holmes syndrome 10.1
16 spinocerebellar ataxia, autosomal recessive 16 10.1
17 hypogonadism 10.1
18 dystonia 10.1
19 dysphagia 10.1
20 myoclonus 10.1
21 spastic paraplegia 25, autosomal recessive 10.1 TTBK2 KCNC3
22 cerebral palsy 10.0 SPTBN2 KCNC3 ITPR1
23 hydrocephalus 10.0
24 movement disease 10.0
25 pathologic nystagmus 10.0
26 spastic paraplegia 34, x-linked 10.0 TTBK2 KCNC3
27 episodic ataxia, type 2 10.0 SPTBN2 KCNC3 ITPR1
28 mucopolysaccharidosis, type vi 10.0 SUMF1 BLOC1S1
29 cerebral palsy, ataxic, autosomal recessive 9.8 SUMF1 SPTBN2 KCNC3 ITPR1
30 spinocerebellar ataxia 13 9.8 TTBK2 SPTBN2 KCNC3
31 spinocerebellar ataxia 18 9.7 TTBK2 SPTBN2 AFG3L2
32 spinocerebellar ataxia, autosomal recessive 8 9.7 SPTBN2 SACS
33 spastic paraplegia 7, autosomal recessive 9.7 SACS AFG3L2
34 marinesco-sjogren syndrome 9.7 SACS KCNC3
35 ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 9.6 SPTBN2 SACS
36 spinocerebellar ataxia 30 9.6 TTBK2 SPTBN2 ITPR1 AFG3L2
37 autosomal recessive cerebellar ataxia 9.6 SPTBN2 SACS BLOC1S1
38 spinocerebellar ataxia, autosomal recessive 14 9.5 SPTBN2 SACS AFG3L2
39 3-methylglutaconic aciduria, type iii 9.5 KCNC3 BLOC1S1 AFG3L2
40 episodic ataxia 9.3 TTBK2 SPTBN2 KCNC3 ITPR1 AFG3L2
41 spinocerebellar ataxia 21 9.3 TTBK2 SPTBN2 KCNC3 CNTN4 AFG3L2
42 cerebellar disease 9.1 SPTBN2 SACS KCNC3 ITPR1 AFG3L2

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:

58 31 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
2 gait ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002066
3 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001272
4 head tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002346
5 upper limb postural tremor 58 31 frequent (33%) Frequent (79-30%) HP:0007351
6 ataxia 58 Very frequent (99-80%)
7 dysarthria 31 HP:0001260
8 scanning speech 31 HP:0002168
9 limb ataxia 31 HP:0002070
10 truncal ataxia 31 HP:0002078
11 dysmetric saccades 31 HP:0000641
12 impaired smooth pursuit 31 HP:0007772
13 postural tremor 31 HP:0002174
14 action tremor 58 Frequent (79-30%)
15 gaze-evoked horizontal nystagmus 31 HP:0007979
16 tremor by anatomical site 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
dysarthria
gait ataxia
cerebellar atrophy
scanning speech
more
Head And Neck Eyes:
dysmetric saccades
impaired smooth pursuit
nystagmus, horizontal, gaze-evoked

Clinical features from OMIM:

606658

UMLS symptoms related to Spinocerebellar Ataxia 15:


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

MGI Mouse Phenotypes related to Spinocerebellar Ataxia 15:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.23 AFG3L2 CNTN4 DNAJC30 ITPR1 KCNC3 SPTBN2

Drugs & Therapeutics for Spinocerebellar Ataxia 15

Search Clinical Trials , 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 Type 16 29 ITPR1

Anatomical Context for Spinocerebellar Ataxia 15

MalaCards organs/tissues related to Spinocerebellar Ataxia 15:

40
Eye, Brain, Cerebellum, Spinal Cord, Testes

Publications for Spinocerebellar Ataxia 15

Articles related to Spinocerebellar Ataxia 15:

(show all 49)
# Title Authors PMID Year
1
Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. 61 56 54 24 6
18579805 2008
2
Heterozygous deletion of ITPR1, but not SUMF1, in spinocerebellar ataxia type 16. 61 6 56 24
17932120 2008
3
Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. 54 61 24 56
17590087 2007
4
Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus. 6 61 56
14981189 2004
5
Spinocerebellar ataxia type 15: diagnostic assessment, frequency, and phenotypic features. 24 56 61
21367767 2011
6
SCA15 due to large ITPR1 deletions in a cohort of 333 white families with dominant ataxia. 61 56 24
21555639 2011
7
Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant. 54 61 56
12828938 2003
8
A new autosomal dominant pure cerebellar ataxia. 24 56
11723290 2001
9
Development of a multiplex ligation-dependent probe amplification assay for diagnosis and estimation of the frequency of spinocerebellar ataxia type 15. 54 24 61
19423733 2009
10
Spinocerebellar Ataxia Type 15 6 61
20301536 2006
11
Prevalence of inositol 1, 4, 5-triphosphate receptor type 1 gene deletion, the mutation for spinocerebellar ataxia type 15, in Japan screened by gene dosage. 24 61
22318346 2012
12
A novel spinocerebellar ataxia type 15 family with involuntary movements and cognitive decline. 24 61
21382133 2011
13
An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description. 24 61
20669319 2010
14
Two Italian families with ITPR1 gene deletion presenting a broader phenotype of SCA15. 61 24
20082166 2010
15
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. 6
20050888 2010
16
"SCA16" is really SCA15. 61 24
18310270 2008
17
The contactin 4 gene locus at 3p26 is a candidate gene of SCA16. 56
17030759 2006
18
Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. 24 61
15623688 2004
19
A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. 56
11445634 2001
20
Hereditary Ataxia Overview 6
20301317 1998
21
Clinical features and classification of inherited ataxias. 56
8421960 1993
22
Classification of the hereditary ataxias and paraplegias. 56
6133167 1983
23
Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia. 24
22986007 2012
24
Sequencing analysis of the ITPR1 gene in a pure autosomal dominant spinocerebellar ataxia series. 61 54
20437544 2010
25
A new dominantly inherited pure cerebellar ataxia, SCA 30. 24
18996908 2009
26
SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. 24
16251216 2006
27
Recent advances in hereditary spinocerebellar ataxias. 24
15804048 2005
28
The wide spectrum of spinocerebellar ataxias (SCAs). 24
15895552 2005
29
Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. 24
15306549 2004
30
Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. 24
15099544 2004
31
Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. 24
14705117 2004
32
The cerebellar cognitive affective syndrome. 24
9577385 1998
33
Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family. 61
29196976 2018
34
A missense variant in ITPR1 provides evidence for autosomal recessive SCA29 with asymptomatic cerebellar hypoplasia in carriers. 61
28488678 2017
35
Spinocerebellar ataxia 15: A phenotypic review and expansion. 61
27908616 2017
36
Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias. 61
26827887 2016
37
Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 gene. 61
25794864 2015
38
[The genetics of spinocerebellar ataxias]. 61
23338152 2013
39
Functional complementation of Drosophila itpr mutants by rat Itpr1. 61
22817477 2012
40
Computational analysis of calcium signaling and membrane electrophysiology in cerebellar Purkinje neurons associated with ataxia. 61
22703638 2012
41
Spinocerebellar ataxia type 15. 61
21827915 2012
42
Role of inositol 1,4,5-trisphosphate receptors in pathogenesis of Huntington's disease and spinocerebellar ataxias. 61
21210219 2011
43
Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family. 61
21689634 2011
44
Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases. 61
21743138 2011
45
Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. 61
21619691 2011
46
Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. 61
20723845 2010
47
Molecular genetic analysis of a new form of spinocerebellar ataxia in a Chinese Han family. 61
20641168 2010
48
[Molecular genetic approach to spinocerebellar ataxias]. 61
20030245 2009
49
Spinocerebellar ataxia type 15. 61
15895559 2005

Variations for Spinocerebellar Ataxia 15

ClinVar genetic disease variations for Spinocerebellar Ataxia 15:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ITPR1 , ITPR1-DT , LOC112935931 , LOC112935932 , SETMAR , SUMF1 deletion Pathogenic 560157 3:4134224-4665869 3:4092540-4624185
2 ITPR1 NC_000003.12:g.(4480596_4480597)_(4793914_4793915)deldeletion Pathogenic 14800 3:4480596-4793915
3 ITPR1 NM_002222.6(ITPR1):c.3176C>T (p.Pro1059Leu)SNV Pathogenic 14801 rs121912425 3:4725156-4725156 3:4683472-4683472
4 ITPR1 NM_002222.6(ITPR1):c.7595G>A (p.Gly2532Glu)SNV Pathogenic 224119 rs869312685 3:4856819-4856819 3:4815135-4815135
5 ITPR1 NM_002222.6(ITPR1):c.805C>T (p.Arg269Trp)SNV Pathogenic/Likely pathogenic 265201 rs886039392 3:4687362-4687362 3:4645678-4645678
6 ITPR1 NM_002222.6(ITPR1):c.3822C>T (p.Asn1274=)SNV Conflicting interpretations of pathogenicity 289460 rs182840163 3:4732893-4732893 3:4691209-4691209
7 ITPR1 NM_001168272.1(ITPR1):c.3619G>A (p.Ala1207Thr)SNV Uncertain significance 447584 rs372881053 3:4726852-4726852 3:4685168-4685168
8 ITPR1 NM_002222.6(ITPR1):c.3179C>T (p.Pro1060Leu)SNV Uncertain significance 517142 rs1467772045 3:4725159-4725159 3:4683475-4683475
9 ITPR1 NM_002222.6(ITPR1):c.7459G>A (p.Gly2487Arg)SNV Uncertain significance 520945 rs1553757628 3:4856193-4856193 3:4814509-4814509
10 ITPR1 NM_002222.6(ITPR1):c.4261G>A (p.Val1421Met)SNV not provided 585154 rs1559718601 3:4738882-4738882 3:4697198-4697198

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

73
# Symbol AA change Variation ID SNP ID
1 ITPR1 p.Pro1083Leu VAR_081167 rs121912425

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 11.05 SPTBN2 KCNC3 ITPR1 AFG3L2

GO Terms for Spinocerebellar Ataxia 15

Biological processes related to Spinocerebellar Ataxia 15 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuron projection development GO:0031175 8.8 PQBP1 CNTN4 BLOC1S1

Sources for Spinocerebellar Ataxia 15

3 CDC
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11 DGIdb
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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