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 42 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) SPTBN2 [HSA:6712] [KO:K06115]
(SCA6) CACNA1A (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 [HSA:146057] [KO:K08815]
(SCA12) PPP2R2B (CAG repeat expansion) [HSA:5521] [KO:K04354]
(SCA13) KCNC3 [HSA:3748] [KO:K04889]
(SCA14) PRKCG [HSA:5582] [KO:K19663]
(SCA15) ITPR1 (deletion) [HSA:3708] [KO:K04958]
(SCA17) TBP (CAG repeat expansion) [HSA:6908] [KO:K03120]
(SCA19/22) KCND3 [HSA:3752] [KO:K04893]
(SCA21) TMEM240 [HSA:339453]
(SCA23) PDYN [HSA:5173] [KO:K15840]
(SCA26) EEF2 [HSA:1938] [KO:K03234]
(SCA27) FGF14 [HSA:2259] [KO:K04358]
(SCA28) AFG3L2 [HSA:10939] [KO:K08956]
(SCA31) BEAN1 [HSA:146227] [KO:K19324]
(SCA35) TGM6 [HSA:343641] [KO:K05624]
(SCA36) NOP56 [HSA:10528] [KO:K14564]
(SCA38) ELOVL5 [HSA:60481] [KO:K10244]
(SCA40) CCDC88C [HSA:440193]
(SCA41) TRPC3 [HSA:7222] [KO:K04966]
(SCA42) CACNA1G [HSA:8913] [KO:K04854]
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)
DOI:10.1097/WNF.0b013e31818736a9
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)
DOI:10.1097/WCO.0b013e3282f7673d
Reference
  Authors
Soong BW, Paulson HL
  Title
Spinocerebellar ataxias: an update.
  Journal
Curr Opin Neurol 20:438-46 (2007)
DOI:10.1097/WCO.0b013e3281fbd3dd
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)
DOI:10.1371/journal.pgen.0030108
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)
DOI:10.1055/s-2007-971172
Reference
PMID:16927298 (SCA5)
  Authors
Bauer P, Schols L, Riess O
  Title
Spectrin mutations in spinocerebellar ataxia (SCA).
  Journal
Bioessays 28:785-7 (2006)
DOI:10.1002/bies.20443
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)
DOI:10.1111/j.1600-0404.2005.00405.x
Reference
PMID:14585172 (gene)
  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)
DOI:10.1017/S1462399403006598
Reference
  Authors
Albin RL
  Title
Dominant ataxias and Friedreich ataxia: an update.
  Journal
Curr Opin Neurol 16:507-14 (2003)
DOI:10.1097/01.wco.0000084230.82329.d5
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)
DOI:10.1007/s004150050456
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)
DOI:10.1016/j.ajhg.2011.05.015
Reference
PMID:23280838 (gene)
  Authors
Duarri A, Jezierska J, Fokkens M, Meijer M, Schelhaas HJ, den Dunnen WF, van Dijk F, Verschuuren-Bemelmans C, Hageman G, van de Vlies P, Kusters B, van de Warrenburg BP, Kremer B, Wijmenga C, Sinke RJ, Swertz MA, Kampinga HH, Boddeke E, Verbeek DS
  Title
Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19.
  Journal
Ann Neurol 72:870-80 (2012)
DOI:10.1002/ana.23700
Reference
PMID:25070513 (gene)
  Authors
Delplanque J, Devos D, Huin V, Genet A, Sand O, Moreau C, Goizet C, Charles P, Anheim M, Monin ML, Buee L, Destee A, Grolez G, Delmaire C, Dujardin K, Dellacherie D, Brice A, Stevanin G, Strubi-Vuillaume I, Durr A, Sablonniere B
  Title
TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment.
  Journal
Brain 137:2657-63 (2014)
DOI:10.1093/brain/awu202
Reference
PMID:23001565 (gene)
  Authors
Hekman KE, Yu GY, Brown CD, Zhu H, Du X, Gervin K, Undlien DE, Peterson A, Stevanin G, Clark HB, Pulst SM, Bird TD, White KP, Gomez CM
  Title
A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity  and increased susceptibility to proteostatic insult.
  Journal
Hum Mol Genet 21:5472-83 (2012)
DOI:10.1093/hmg/dds392
Reference
PMID:25253745 (gene)
  Authors
Guo YC, Lin JJ, Liao YC, Tsai PC, Lee YC, Soong BW
  Title
Spinocerebellar ataxia 35: novel mutations in TGM6 with clinical and genetic characterization.
  Journal
Neurology 83:1554-61 (2014)
DOI:10.1212/WNL.0000000000000909
Reference
PMID:25065913 (gene)
  Authors
Di Gregorio E, Borroni B, Giorgio E, Lacerenza D, Ferrero M, Lo Buono N, Ragusa N, Mancini C, Gaussen M, Calcia A, Mitro N, Hoxha E, Mura I, Coviello DA, Moon YA, Tesson C, Vaula G, Couarch P, Orsi L, Duregon E, Papotti MG, Deleuze JF, Imbert J, Costanzi C, Padovani A, Giunti P, Maillet-Vioud M, Durr A, Brice A, Tempia F, Funaro A, Boccone L, Caruso D, Stevanin G, Brusco A
  Title
ELOVL5 mutations cause spinocerebellar ataxia 38.
  Journal
Am J Hum Genet 95:209-17 (2014)
DOI:10.1016/j.ajhg.2014.07.001
Reference
PMID:25062847 (gene)
  Authors
Tsoi H, Yu AC, Chen ZS, Ng NK, Chan AY, Yuen LY, Abrigo JM, Tsang SY, Tsui SK, Tong TM, Lo IF, Lam ST, Mok VC, Wong LK, Ngo JC, Lau KF, Chan TF, Chan HY
  Title
A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia.
  Journal
J Med Genet 51:590-5 (2014)
DOI:10.1136/jmedgenet-2014-102333
Reference
PMID:21321808 (gene)
  Authors
Becker EB, Fogel BL, Rajakulendran S, Dulneva A, Hanna MG, Perlman SL, Geschwind DH, Davies KE
  Title
Candidate screening of the TRPC3 gene in cerebellar ataxia.
  Journal
Cerebellum 10:296-9 (2011)
DOI:10.1007/s12311-011-0253-6
Reference
PMID:11927664 (gene)
  Authors
Chemin J, Monteil A, Perez-Reyes E, Bourinet E, Nargeot J, Lory P
  Title
Specific contribution of human T-type calcium channel isotypes (alpha(1G), alpha(1H) and alpha(1I)) to neuronal excitability.
  Journal
J Physiol 540:3-14 (2002)

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