KEGG   DISEASE: Spinocerebellar ataxia (SCA)Help
Entry
H00063                      Disease                                

Name
Spinocerebellar ataxia (SCA)
Description
The dominantly inherited ataxias or spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of progressive disorders which characteraized by cerebellar ataxia, seizures, eyes/oculomotor deficits, gait ataxia and dysarthria ataxia.The prevalence of SCAs is estimated to be 1-4/100.000. At least 28 genetic loci for SCAs had been discovered. SCA1, 2, 3, 6, 7 and 17 are caused by CAG repeat expansions that encode a pure repeat of the amino acid glutamine in the disease protein. SCA8, 10 and 12 are due to repeat expansions outside of the protein-coding region of the respective disease genes. SCA5, 13, 14 and 27 are caused by conventional mutations in specific genes: deletion, missense, nonsense and splice site mutations.
Category
Neurodegenerative disease
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00063  Spinocerebellar ataxia (SCA)
Human diseases in ICD-10 classification [BR:br08403]
 6. Diseases of the nervous system (G00-G99)
  G30-G32  Other degenerative diseases of the nervous system
   G31  Other degenerative diseases of nervous system, not elsewhere classified
    H00063  Spinocerebellar ataxia
BRITE hierarchy
Pathway
Long-term depression
Ribosome biogenesis in eukaryotes
Gene
(SCA1) ATXN1 (CAG repeat expansion) [HSA:6310]
(SCA2) ATXN2 (CAG repeat expansion) [HSA:6311]
(SCA3) ATXN3 (CAG repeat expansion) [HSA:4287] [KO:K11863]
(SCA5/ SCAR14) SPTBN2; spectrin, beta, non-erythrocytic 2 (mutation) [HSA:6712] [KO:K06115]
(SCA6) CACNA1A; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit (CAG repeat expansion) [HSA:773] [KO:K04344]
(SCA7) ATXN7 (CAG repeat expansion) [HSA:6314] [KO:K11318]
(SCA8) ATXN8 opposite strand (CTG/CAG repeat expansion)
(SCA10) ATXN10 (ATTCT repeat expansion) [HSA:25814] [KO:K19323]
(SCA11) TTBK2; tau tubulin kinase 2 (mutation) [HSA:146057] [KO:K08815]
(SCA12) PPP2R2B; protein phosphatase 2 (CAG repeat expansion) [HSA:5521] [KO:K04354]
(SCA13) KCNC3; potassium voltage-gated channel, Shaw-related subfamily, member 3 (mutation) [HSA:3748] [KO:K04889]
(SCA14) PRKCG; protein kinase C, gamma (mutation) [HSA:5582] [KO:K19663]
(SCA15) ITPR1; inositol 1,4,5-triphosphate receptor, type 1 (deletion) [HSA:3708] [KO:K04958]
(SCA17) TBP; TATA box binding protein (CAG repeat expansion) [HSA:6908] [KO:K03120]
(SCA23) PDYN; prodynorphin [HSA:5173] [KO:K15840]
(SCA27) FGF14; fibroblast growth factor 14 (mutation) [HSA:2259] [KO:K04358]
(SCA28) AFG3L2; AFG3 ATPase family gene 3-like 2 [HSA:10939] [KO:K08956]
(SCA31) BEAN1; brain expressed, associated with NEDD4, 1 [HSA:146227] [KO:K19324]
(SCA36) NOP56 [HSA:10528] [KO:K14564]
(SCAR5) ZNF592 [HSA:9640] [KO:K19325]
(SCAR8) SYNE1 [HSA:23345] [KO:K19326]
(SCAR9) ADCK3 [HSA:56997] [KO:K08869]
(SCAR10) ANO10 [HSA:55129] [KO:K19327]
(SCAR11) SYT14 [HSA:255928] [KO:K19328]
(SCAR12) WWOX [HSA:51741] [KO:K19329]
(SCAR13) GRM1 [HSA:2911] [KO:K04603]
(SCAR15) KIAA0226 [HSA:9711] [KO:K19330]
(SCAR16) STUB1 [HSA:10273] [KO:K09561]
(SCAN1) TDP1 [HSA:55775] [KO:K10862]
Drug
(SCA3/SCA14) Chantix [DR:D06282]
(SCA3) Lamictal [DR:D00354]
Comment
Disease class: polyglutamine disease
Affected region: cerebellum, dentate nucleus, brain stem (SCA1); cerebellum, brain stem, frontotemporal lobes (frontal lobe and temporal lobe) (SCA2); cerebellum, basal ganglia, brain stem, spinal cord (SCA3); cerebellum (SCA5); cerebellum, dentate nucleus, inferior olive (SCA6); cerebellum, inferior olive, dentate nucleus, pontine nuclei (also the retina) (SCA7); cerebral cortex, cerebellum (SCA12); cerebellum, inferior olive (SCA17)
Microscopic lesion: neuronal inclusions (SCA1, SCA2, SCA3, SCA7, SCA17); cytoplasmic inclusions (SCA6)
See also H01478 Machado-Joseph disease.
Other DBs
Reference
PMID:19050414 (drug)
  Authors
Zesiewicz TA, Sullivan KL
  Title
Treatment of ataxia and imbalance with varenicline (chantix): report of 2 patients with spinocerebellar ataxia (types 3 and 14).
  Journal
Clin Neuropharmacol 31:363-5 (2008)
Reference
PMID:18317266 (SCA3)
  Authors
Rub U, Brunt ER, Deller T
  Title
New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado-Joseph disease).
  Journal
Curr Opin Neurol 21:111-6 (2008)
Reference
  Authors
Soong BW, Paulson HL
  Title
Spinocerebellar ataxias: an update.
  Journal
Curr Opin Neurol 20:438-46 (2007)
Reference
PMID:17590087 (SCA15)
  Authors
van de Leemput J, Chandran J, Knight MA, Holtzclaw LA, Scholz S, Cookson MR, Houlden H, Gwinn-Hardy K, Fung HC, Lin X, Hernandez D, Simon-Sanchez J, Wood NW, Giunti P, Rafferty I, Hardy J, Storey E, Gardner RJ, Forrest SM, Fisher EM, Russell JT, Cai H, Singleton AB
  Title
Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans.
  Journal
PLoS Genet 3:e108 (2007)
Reference
PMID:17390258 (SCA3)
  Authors
Paulson HL
  Title
Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3.
  Journal
Semin Neurol 27:133-42 (2007)
Reference
PMID:16927298 (SCA5)
  Authors
Bauer P, Schols L, Riess O
  Title
Spectrin mutations in spinocerebellar ataxia (SCA).
  Journal
Bioessays 28:785-7 (2006)
Reference
PMID:15876340 (Drug)
  Authors
Liu CS, Hsu HM, Cheng WL, Hsieh M
  Title
Clinical and molecular events in patients with Machado-Joseph disease under lamotrigine therapy.
  Journal
Acta Neurol Scand 111:385-90 (2005)
Reference
  Authors
Rudnicki DD, Margolis RL.
  Title
Repeat expansion and autosomal dominant neurodegenerative disorders: consensus and controversy.
  Journal
Expert Rev Mol Med 5:1-24 (2003)
Reference
  Authors
Albin RL
  Title
Dominant ataxias and Friedreich ataxia: an update.
  Journal
Curr Opin Neurol 16:507-14 (2003)
Reference
PMID:10525976 (SCA1, SCA2, SCA3)
  Authors
Burk K, Fetter M, Abele M, Laccone F, Brice A, Dichgans J, Klockgether T
  Title
Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3.
  Journal
J Neurol 246:789-97 (1999)
Reference
  Authors
Nicolas E, Poitelon Y, Chouery E, Salem N, Levy N, Megarbane A, Delague V
  Title
CAMOS, a nonprogressive, autosomal recessive, congenital cerebellar ataxia, is caused by a mutant zinc-finger protein, ZNF592.
  Journal
Eur J Hum Genet 18:1107-13 (2010)
Reference
  Authors
Gros-Louis F, Dupre N, Dion P, Fox MA, Laurent S, Verreault S, Sanes JR, Bouchard JP, Rouleau GA
  Title
Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia.
  Journal
Nat Genet 39:80-5 (2007)
Reference
  Authors
Lagier-Tourenne C, Tazir M, Lopez LC, Quinzii CM, Assoum M, Drouot N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koenig M
  Title
ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.
  Journal
Am J Hum Genet 82:661-72 (2008)
Reference
  Authors
Vermeer S, Hoischen A, Meijer RP, Gilissen C, Neveling K, Wieskamp N, de Brouwer A, Koenig M, Anheim M, Assoum M, Drouot N, Todorovic S, Milic-Rasic V, Lochmuller H, Stevanin G, Goizet C, David A, Durr A, Brice A, Kremer B, van de Warrenburg BP, Schijvenaars MM, Heister A, Kwint M, Arts P, van der Wijst J, Veltman J, Kamsteeg EJ, Scheffer H, Knoers N
  Title
Targeted next-generation sequencing of a 12.5 Mb homozygous region reveals ANO10  mutations in patients with autosomal-recessive cerebellar ataxia.
  Journal
Am J Hum Genet 87:813-9 (2010)
Reference
  Authors
Hirano R, Interthal H, Huang C, Nakamura T, Deguchi K, Choi K, Bhattacharjee MB, Arimura K, Umehara F, Izumo S, Northrop JL, Salih MA, Inoue K, Armstrong DL, Champoux JJ, Takashima H, Boerkoel CF
  Title
Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?
  Journal
EMBO J 26:4732-43 (2007)
Reference
PMID:22901947 (SCAR13)
  Authors
Guergueltcheva V, Azmanov DN, Angelicheva D, Smith KR, Chamova T, Florez L, Bynevelt M, Nguyen T, Cherninkova S, Bojinova V, Kaprelyan A, Angelova L, Morar B, Chandler D, Kaneva R, Bahlo M, Tournev I, Kalaydjieva L
  Title
Autosomal-recessive congenital cerebellar ataxia is caused by mutations in metabotropic glutamate receptor 1.
  Journal
Am J Hum Genet 91:553-64 (2012)
Reference
  Authors
Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A
  Title
Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type  of spinocerebellar ataxia accompanied by motor neuron involvement.
  Journal
Am J Hum Genet 89:121-30 (2011)
Reference
  Authors
Doi H, Yoshida K, Yasuda T, Fukuda M, Fukuda Y, Morita H, Ikeda S, Kato R, Tsurusaki Y, Miyake N, Saitsu H, Sakai H, Miyatake S, Shiina M, Nukina N, Koyano S, Tsuji S, Kuroiwa Y, Matsumoto N
  Title
Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation.
  Journal
Am J Hum Genet 89:320-7 (2011)
Reference
PMID:20826435 (SCAR15)
  Authors
Assoum M, Salih MA, Drouot N, H'Mida-Ben Brahim D, Lagier-Tourenne C, AlDrees A, Elmalik SA, Ahmed TS, Seidahmed MZ, Kabiraj MM, Koenig M
  Title
Rundataxin, a novel protein with RUN and diacylglycerol binding domains, is mutant in a new recessive ataxia.
  Journal
Brain 133:2439-47 (2010)
Reference
  Authors
Shi Y, Wang J, Li JD, Ren H, Guan W, He M, Yan W, Zhou Y, Hu Z, Zhang J, Xiao J, Su Z, Dai M, Wang J, Jiang H, Guo J, Zhou Y, Zhang F, Li N, Du J, Xu Q, Hu Y, Pan Q, Shen L, Wang G, Xia K, Zhang Z, Tang B
  Title
Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia.
  Journal
PLoS One 8:e81884 (2013)
Reference
  Authors
Mallaret M, Synofzik M, Lee J, Sagum CA, Mahajnah M, Sharkia R, Drouot N, Renaud M, Klein FA, Anheim M, Tranchant C, Mignot C, Mandel JL, Bedford M, Bauer P, Salih MA, Schule R, Schols L, Aldaz CM, Koenig M
  Title
The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation.
  Journal
Brain 137:411-9 (2014)

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