Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

The spinocerebellar ataxias

Puneet Opal, MD, PhD
Huda Y Zoghbi, MD
Section Editors
Marc C Patterson, MD, FRACP
Helen V Firth, DM, FRCP, DCH
Deputy Editor
John F Dashe, MD, PhD


Numerous classification systems have been proposed for the autosomal dominant ataxias, which are distinct from the autosomal recessive disorder, Friedreich ataxia. (See "Friedreich ataxia".)

One system proposed by Anita Harding divided these disorders into autosomal dominant cerebellar ataxia types I, II, and III [1,2]:

Type I syndromes are ataxias with ophthalmoplegia, optic atrophy, dementia and extrapyramidal features (ie, SCA1-SCA4, SCA8, SCA10, SCA12-SCA23, SCA25, SCA27, SCA28, and dentatorubral pallidoluysian atrophy or DRPLA)

Type II ataxias are associated with pigmented maculopathy with or without ophthalmoplegia or extrapyramidal features (ie, SCA7)

Type III syndromes are pure ataxic syndromes (ie, SCA5, SCA6, SCA11, SCA26, SCA29, SCA30, and SCA31)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jan 06, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Harding AE. Clinical features and classification of inherited ataxias. Adv Neurol 1993; 61:1.
  2. Whaley NR, Fujioka S, Wszolek ZK. Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis 2011; 6:33.
  3. Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 2005; 4:2.
  4. Schöls L, Szymanski S, Peters S, et al. Genetic background of apparently idiopathic sporadic cerebellar ataxia. Hum Genet 2000; 107:132.
  5. Trottier Y, Lutz Y, Stevanin G, et al. Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature 1995; 378:403.
  6. Jacobi H, Bauer P, Giunti P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology 2011; 77:1035.
  7. Rüb U, Bürk K, Schöls L, et al. Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3. Neurology 2004; 63:1258.
  8. Klockgether T, Lüdtke R, Kramer B, et al. The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain 1998; 121 ( Pt 4):589.
  9. Bird TD. Hereditary ataxia overview. In: GeneReviews [Internet]. www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ataxias (Accessed on September 29, 2011).
  10. Clauss R, Sathekge M, Nel W. Transient improvement of spinocerebellar ataxia with zolpidem. N Engl J Med 2004; 351:511.
  11. Zesiewicz TA, Greenstein PE, Sullivan KL, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology 2012; 78:545.
  12. Cummings CJ, Mancini MA, Antalffy B, et al. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat Genet 1998; 19:148.
  13. Kazemi-Esfarjani P, Benzer S. Genetic suppression of polyglutamine toxicity in Drosophila. Science 2000; 287:1837.
  14. Warrick JM, Chan HY, Gray-Board GL, et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat Genet 1999; 23:425.
  15. Xia H, Mao Q, Eliason SL, et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med 2004; 10:816.
  16. Tang B, Liu C, Shen L, et al. Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Arch Neurol 2000; 57:540.
  17. Geschwind DH, Perlman S, Figueroa CP, et al. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet 1997; 60:842.
  18. Moseley ML, Benzow KA, Schut LJ, et al. Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 1998; 51:1666.
  19. Storey E, du Sart D, Shaw JH, et al. Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia. Am J Med Genet 2000; 95:351.
  20. Ranum LP, Lundgren JK, Schut LJ, et al. Spinocerebellar ataxia type 1 and Machado-Joseph disease: incidence of CAG expansions among adult-onset ataxia patients from 311 families with dominant, recessive, or sporadic ataxia. Am J Hum Genet 1995; 57:603.
  21. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007; 30:575.
  22. Orr HT, Chung MY, Banfi S, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 1993; 4:221.
  23. Skinner PJ, Koshy BT, Cummings CJ, et al. Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature 1997; 389:971.
  24. Klement IA, Skinner PJ, Kaytor MD, et al. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 1998; 95:41.
  25. Zoghbi HY, Orr HT. Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1. J Biol Chem 2009; 284:7425.
  26. de Chiara C, Giannini C, Adinolfi S, et al. The AXH module: an independently folded domain common to ataxin-1 and HBP1. FEBS Lett 2003; 551:107.
  27. Gehrking KM, Andresen JM, Duvick L, et al. Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genet 2011; 20:2204.
  28. Lam YC, Bowman AB, Jafar-Nejad P, et al. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell 2006; 127:1335.
  29. Emamian ES, Kaytor MD, Duvick LA, et al. Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 2003; 38:375.
  30. Lim J, Crespo-Barreto J, Jafar-Nejad P, et al. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 2008; 452:713.
  31. Orr HT. SCA1-phosphorylation, a regulator of Ataxin-1 function and pathogenesis. Prog Neurobiol 2012; 99:179.
  32. Park J, Al-Ramahi I, Tan Q, et al. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature 2013; 498:325.
  33. Lorenzetti D, Bohlega S, Zoghbi HY. The expansion of the CAG repeat in ataxin-2 is a frequent cause of autosomal dominant spinocerebellar ataxia. Neurology 1997; 49:1009.
  34. Orozco Diaz G, Nodarse Fleites A, Cordovés Sagaz R, Auburger G. Autosomal dominant cerebellar ataxia: clinical analysis of 263 patients from a homogeneous population in Holguín, Cuba. Neurology 1990; 40:1369.
  35. Pulst SM, Nechiporuk A, Nechiporuk T, et al. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet 1996; 14:269.
  36. Sanpei K, Takano H, Igarashi S, et al. Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet 1996; 14:277.
  37. Huynh DP, Figueroa K, Hoang N, Pulst SM. Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human. Nat Genet 2000; 26:44.
  38. Imbert G, Saudou F, Yvert G, et al. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 1996; 14:285.
  39. Paciorkowski AR, Shafrir Y, Hrivnak J, et al. Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms. Neurology 2011; 77:1055.
  40. Singh A, Faruq M, Mukerji M, et al. Infantile onset spinocerebellar ataxia 2 (SCA2): a clinical report with review of previous cases. J Child Neurol 2014; 29:139.
  41. Fernandez M, McClain ME, Martinez RA, et al. Late-onset SCA2: 33 CAG repeats are sufficient to cause disease. Neurology 2000; 55:569.
  42. Velázquez-Pérez L, Seifried C, Santos-Falcón N, et al. Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2. Ann Neurol 2004; 56:444.
  43. Gwinn-Hardy K, Chen JY, Liu HC, et al. Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese. Neurology 2000; 55:800.
  44. Babovic-Vuksanovic D, Snow K, Patterson MC, Michels VV. Spinocerebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat expansion. Am J Med Genet 1998; 79:383.
  45. Malandrini A, Galli L, Villanova M, et al. CAG repeat expansion in an italian family with spinocerebellar ataxia type 2 (SCA2): a clinical and genetic study. Eur Neurol 1998; 40:164.
  46. Belal S, Cancel G, Stevanin G, et al. Clinical and genetic analysis of a Tunisian family with autosomal dominant cerebellar ataxia type 1 linked to the SCA2 locus. Neurology 1994; 44:1423.
  47. Dürr A, Smadja D, Cancel G, et al. Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies). Clinical and neuropathological analysis of 53 patients from three unrelated SCA2 families. Brain 1995; 118 ( Pt 6):1573.
  48. Kawaguchi Y, Okamoto T, Taniwaki M, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 1994; 8:221.
  49. Higgins JJ, Nee LE, Vasconcelos O, et al. Mutations in American families with spinocerebellar ataxia (SCA) type 3: SCA3 is allelic to Machado-Joseph disease. Neurology 1996; 46:208.
  50. Tait D, Riccio M, Sittler A, et al. Ataxin-3 is transported into the nucleus and associates with the nuclear matrix. Hum Mol Genet 1998; 7:991.
  51. Warrick JM, Paulson HL, Gray-Board GL, et al. Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 1998; 93:939.
  52. Ikeda H, Yamaguchi M, Sugai S, et al. Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat Genet 1996; 13:196.
  53. França MC Jr, D'Abreu A, Nucci A, Lopes-Cendes I. Muscle excitability abnormalities in Machado-Joseph disease. Arch Neurol 2008; 65:525.
  54. Kawai Y, Takeda A, Abe Y, et al. Cognitive impairments in Machado-Joseph disease. Arch Neurol 2004; 61:1757.
  55. Yeh TH, Lu CS, Chou YH, et al. Autonomic dysfunction in Machado-Joseph disease. Arch Neurol 2005; 62:630.
  56. Pedroso JL, França MC Jr, Braga-Neto P, et al. Nonmotor and extracerebellar features in Machado-Joseph disease: a review. Mov Disord 2013; 28:1200.
  57. D'Abreu A, França M Jr, Conz L, et al. Sleep symptoms and their clinical correlates in Machado-Joseph disease. Acta Neurol Scand 2009; 119:277.
  58. Flanigan K, Gardner K, Alderson K, et al. Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Am J Hum Genet 1996; 59:392.
  59. Nagaoka U, Takashima M, Ishikawa K, et al. A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia. Neurology 2000; 54:1971.
  60. Stevanin G, Herman A, Brice A, Dürr A. Clinical and MRI findings in spinocerebellar ataxia type 5. Neurology 1999; 53:1355.
  61. Jacob FD, Ho ES, Martinez-Ojeda M, et al. Case of infantile onset spinocerebellar ataxia type 5. J Child Neurol 2013; 28:1292.
  62. Ranum LP, Schut LJ, Lundgren JK, et al. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet 1994; 8:280.
  63. Ikeda Y, Dick KA, Weatherspoon MR, et al. Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet 2006; 38:184.
  64. Gomez CM, Thompson RM, Gammack JT, et al. Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset. Ann Neurol 1997; 42:933.
  65. Stevanin G, Dürr A, David G, et al. Clinical and molecular features of spinocerebellar ataxia type 6. Neurology 1997; 49:1243.
  66. Matsumura R, Futamura N, Fujimoto Y, et al. Spinocerebellar ataxia type 6. Molecular and clinical features of 35 Japanese patients including one homozygous for the CAG repeat expansion. Neurology 1997; 49:1238.
  67. Craig K, Keers SM, Archibald K, et al. Molecular epidemiology of spinocerebellar ataxia type 6. Ann Neurol 2004; 55:752.
  68. Zhuchenko O, Bailey J, Bonnen P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 1997; 15:62.
  69. Restituito S, Thompson RM, Eliet J, et al. The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta subunit-specific enhanced activation of P/Q-type calcium channels in Xenopus oocytes. J Neurosci 2000; 20:6394.
  70. Ishikawa K, Fujigasaki H, Saegusa H, et al. Abundant expression and cytoplasmic aggregations of [alpha]1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6. Hum Mol Genet 1999; 8:1185.
  71. Ophoff RA, Terwindt GM, Vergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996; 87:543.
  72. Terwindt GM, Ophoff RA, Haan J, et al. Variable clinical expression of mutations in the P/Q-type calcium channel gene in familial hemiplegic migraine. Dutch Migraine Genetics Research Group. Neurology 1998; 50:1105.
  73. Benton CS, de Silva R, Rutledge SL, et al. Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype. Neurology 1998; 51:1081.
  74. Ansorge O, Giunti P, Michalik A, et al. Ataxin-7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats. Ann Neurol 2004; 56:448.
  75. Gouw LG, Kaplan CD, Haines JH, et al. Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p. Nat Genet 1995; 10:89.
  76. David G, Abbas N, Stevanin G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 1997; 17:65.
  77. Stevanin G, Giunti P, Belal GD, et al. De novo expansion of intermediate alleles in spinocerebellar ataxia 7. Hum Mol Genet 1998; 7:1809.
  78. Lindenberg KS, Yvert G, Müller K, Landwehrmeyer GB. Expression analysis of ataxin-7 mRNA and protein in human brain: evidence for a widespread distribution and focal protein accumulation. Brain Pathol 2000; 10:385.
  79. Yvert G, Lindenberg KS, Picaud S, et al. Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice. Hum Mol Genet 2000; 9:2491.
  80. Day JW, Schut LJ, Moseley ML, et al. Spinocerebellar ataxia type 8: clinical features in a large family. Neurology 2000; 55:649.
  81. Juvonen V, Hietala M, Päivärinta M, et al. Clinical and genetic findings in Finnish ataxia patients with the spinocerebellar ataxia 8 repeat expansion. Ann Neurol 2000; 48:354.
  82. Ito H, Kawakami H, Wate R, et al. Clinicopathologic investigation of a family with expanded SCA8 CTA/CTG repeats. Neurology 2006; 67:1479.
  83. Todd PK, Paulson HL. RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol 2010; 67:291.
  84. Koob MD, Moseley ML, Schut LJ, et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 1999; 21:379.
  85. Silveira I, Alonso I, Guimarães L, et al. High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles. Am J Hum Genet 2000; 66:830.
  86. Moseley ML, Zu T, Ikeda Y, et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 2006; 38:758.
  87. Ikeda Y, Dalton JC, Moseley ML, et al. Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia. Am J Hum Genet 2004; 75:3.
  88. Grewal RP, Achari M, Matsuura T, et al. Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10. Arch Neurol 2002; 59:1285.
  89. Teive HA, Roa BB, Raskin S, et al. Clinical phenotype of Brazilian families with spinocerebellar ataxia 10. Neurology 2004; 63:1509.
  90. Gatto EM, Gao R, White MC, et al. Ethnic origin and extrapyramidal signs in an Argentinean spinocerebellar ataxia type 10 family. Neurology 2007; 69:216.
  91. Matsuura T, Achari M, Khajavi M, et al. Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs and epilepsy. Ann Neurol 1999; 45:407.
  92. Zu L, Figueroa KP, Grewal R, Pulst SM. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet 1999; 64:594.
  93. Matsuura T, Yamagata T, Burgess DL, et al. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 2000; 26:191.
  94. Worth PF, Giunti P, Gardner-Thorpe C, et al. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. Am J Hum Genet 1999; 65:420.
  95. Houlden H, Johnson J, Gardner-Thorpe C, et al. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet 2007; 39:1434.
  96. Holmes SE, O'Hearn EE, McInnis MG, et al. Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. Nat Genet 1999; 23:391.
  97. Srivastava AK, Takkar A, Garg A, Faruq M. Clinical behaviour of spinocerebellar ataxia type 12 and intermediate length abnormal CAG repeats in PPP2R2B. Brain 2017; 140:27.
  98. Herman-Bert A, Stevanin G, Netter JC, et al. Mapping of spinocerebellar ataxia 13 to chromosome 19q13.3-q13.4 in a family with autosomal dominant cerebellar ataxia and mental retardation. Am J Hum Genet 2000; 67:229.
  99. Waters MF, Minassian NA, Stevanin G, et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 2006; 38:447.
  100. Yamashita I, Sasaki H, Yabe I, et al. A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter. Ann Neurol 2000; 48:156.
  101. Yabe I, Sasaki H, Chen DH, et al. Spinocerebellar ataxia type 14 caused by a mutation in protein kinase C gamma. Arch Neurol 2003; 60:1749.
  102. Verbeek DS, Knight MA, Harmison GG, et al. Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting. Brain 2005; 128:436.
  103. Chen DH, Cimino PJ, Ranum LP, et al. The clinical and genetic spectrum of spinocerebellar ataxia 14. Neurology 2005; 64:1258.
  104. Klebe S, Durr A, Rentschler A, et al. New mutations in protein kinase Cgamma associated with spinocerebellar ataxia type 14. Ann Neurol 2005; 58:720.
  105. Storey E, Gardner RJ, Knight MA, et al. A new autosomal dominant pure cerebellar ataxia. Neurology 2001; 57:1913.
  106. Miyoshi Y, Yamada T, Tanimura M, et al. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology 2001; 57:96.
  107. Knight MA, Kennerson ML, Anney RJ, et al. Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant. Neurobiol Dis 2003; 13:147.
  108. Hara K, Fukushima T, Suzuki T, et al. Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus. Neurology 2004; 62:648.
  109. van de Leemput J, Chandran J, Knight MA, et al. Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans. PLoS Genet 2007; 3:e108.
  110. Hara K, Shiga A, Nozaki H, et al. Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. Neurology 2008; 71:547.
  111. Iwaki A, Kawano Y, Miura S, et al. Heterozygous deletion of ITPR1, but not SUMF1, in spinocerebellar ataxia type 16. J Med Genet 2008; 45:32.
  112. Gardner RJ. "SCA16" is really SCA15. J Med Genet 2008; 45:192.
  113. Miura S, Shibata H, Furuya H, et al. The contactin 4 gene locus at 3p26 is a candidate gene of SCA16. Neurology 2006; 67:1236.
  114. Nakamura K, Jeong SY, Uchihara T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 2001; 10:1441.
  115. Schneider SA, van de Warrenburg BP, Hughes TD, et al. Phenotypic homogeneity of the Huntington disease-like presentation in a SCA17 family. Neurology 2006; 67:1701.
  116. Friedman MJ, Shah AG, Fang ZH, et al. Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nat Neurosci 2007; 10:1519.
  117. Brkanac Z, Fernandez M, Matsushita M, et al. Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to chromosome 7q22-q32. Am J Med Genet 2002; 114:450.
  118. Schelhaas HJ, Ippel PF, Hageman G, et al. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia. J Neurol 2001; 248:113.
  119. Verbeek DS, Schelhaas JH, Ippel EF, et al. Identification of a novel SCA locus ( SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Hum Genet 2002; 111:388.
  120. Chung MY, Lu YC, Cheng NC, Soong BW. A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain 2003; 126:1293.
  121. Duarri A, Jezierska J, Fokkens M, et al. Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. Ann Neurol 2012; 72:870.
  122. Lee YC, Durr A, Majczenko K, et al. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol 2012; 72:859.
  123. Pulst SM, Otis TS. Repolarization matters: mutations in the Kv4.3 potassium channel cause SCA19/22. Ann Neurol 2012; 72:829.
  124. Knight MA, Gardner RJ, Bahlo M, et al. Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain 2004; 127:1172.
  125. Devos D, Schraen-Maschke S, Vuillaume I, et al. Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology 2001; 56:234.
  126. Delplanque J, Devos D, Huin V, et al. TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. Brain 2014; 137:2657.
  127. Verbeek DS, van de Warrenburg BP, Wesseling P, et al. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain 2004; 127:2551.
  128. Bakalkin G, Watanabe H, Jezierska J, et al. Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet 2010; 87:593.
  129. Swartz BE, Burmeister M, Somers JT, et al. A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus. Ann N Y Acad Sci 2002; 956:441.
  130. Swartz BE, Li S, Bespalova I, et al. Pathogenesis of clinical signs in recessive ataxia with saccadic intrusions. Ann Neurol 2003; 54:824.
  131. Stevanin G, Bouslam N, Thobois S, et al. Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. Ann Neurol 2004; 55:97.
  132. Yu GY, Howell MJ, Roller MJ, et al. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol 2005; 57:349.
  133. Hekman KE, Yu GY, Brown CD, et al. A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult. Hum Mol Genet 2012; 21:5472.
  134. van Swieten JC, Brusse E, de Graaf BM, et al. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet 2003; 72:191.
  135. Brusse E, de Koning I, Maat-Kievit A, et al. Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype. Mov Disord 2006; 21:396.
  136. Dalski A, Atici J, Kreuz FR, et al. Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias. Eur J Hum Genet 2005; 13:118.
  137. Cagnoli C, Mariotti C, Taroni F, et al. SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. Brain 2006; 129:235.
  138. Di Bella D, Lazzaro F, Brusco A, et al. Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet 2010; 42:313.
  139. Dudding TE, Friend K, Schofield PW, et al. Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. Neurology 2004; 63:2288.
  140. Storey E, Bahlo M, Fahey M, et al. A new dominantly inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry 2009; 80:408.
  141. Ishikawa K, Toru S, Tsunemi T, et al. An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains. Am J Hum Genet 2005; 77:280.
  142. Owada K, Ishikawa K, Toru S, et al. A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III. Neurology 2005; 65:629.
  143. Onodera Y, Aoki M, Mizuno H, et al. Clinical features of chromosome 16q22.1 linked autosomal dominant cerebellar ataxia in Japanese. Neurology 2006; 67:1300.
  144. Sato N, Amino T, Kobayashi K, et al. Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n. Am J Hum Genet 2009; 85:544.
  145. Jiang H, Zhu HP, Gomez CM. SCA32: an autosomal dominant cerebellar ataxia with azoospermia maps to chromosome 7q32-q33 [abstract]. Mov Disord 2010; 25:S192.
  146. Giroux JM, Barbeau A. Erythrokeratodermia with ataxia. Arch Dermatol 1972; 106:183.
  147. Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, et al. Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol 2014; 71:470.
  148. Ozaki K, Doi H, Mitsui J, et al. A Novel Mutation in ELOVL4 Leading to Spinocerebellar Ataxia (SCA) With the Hot Cross Bun Sign but Lacking Erythrokeratodermia: A Broadened Spectrum of SCA34. JAMA Neurol 2015; 72:797.
  149. Wang JL, Yang X, Xia K, et al. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 2010; 133:3510.
  150. Li M, Pang SY, Song Y, et al. Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family. Clin Genet 2013; 83:269.
  151. Guo YC, Lin JJ, Liao YC, et al. Spinocerebellar ataxia 35: novel mutations in TGM6 with clinical and genetic characterization. Neurology 2014; 83:1554.
  152. Kobayashi H, Abe K, Matsuura T, et al. Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am J Hum Genet 2011; 89:121.
  153. Ikeda Y, Ohta Y, Kobayashi H, et al. Clinical features of SCA36: a novel spinocerebellar ataxia with motor neuron involvement (Asidan). Neurology 2012; 79:333.
  154. Sugihara K, Maruyama H, Morino H, et al. The clinical characteristics of spinocerebellar ataxia 36: a study of 2121 Japanese ataxia patients. Mov Disord 2012; 27:1158.
  155. García-Murias M, Quintáns B, Arias M, et al. 'Costa da Morte' ataxia is spinocerebellar ataxia 36: clinical and genetic characterization. Brain 2012; 135:1423.
  156. Obayashi M, Stevanin G, Synofzik M, et al. Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion. J Neurol Neurosurg Psychiatry 2015; 86:986.
  157. Serrano-Munuera C, Corral-Juan M, Stevanin G, et al. New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32. JAMA Neurol 2013; 70:764.
  158. Di Gregorio E, Borroni B, Giorgio E, et al. ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet 2014; 95:209.
  159. Tsoi H, Yu AC, Chen ZS, et al. A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia. J Med Genet 2014; 51:590.
  160. Onodera O, Oyake M, Takano H, et al. Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS. Am J Hum Genet 1995; 57:1050.
  161. Egawa K, Takahashi Y, Kubota Y, et al. Electroclinical features of epilepsy in patients with juvenile type dentatorubral-pallidoluysian atrophy. Epilepsia 2008; 49:2041.
  162. Koide R, Onodera O, Ikeuchi T, et al. Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings. Neurology 1997; 49:1605.
  163. Silveira I, Lopes-Cendes I, Kish S, et al. Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients. Neurology 1996; 46:214.
  164. Le Ber I, Camuzat A, Castelnovo G, et al. Prevalence of dentatorubral-pallidoluysian atrophy in a large series of white patients with cerebellar ataxia. Arch Neurol 2003; 60:1097.
  165. Brusco A, Gellera C, Cagnoli C, et al. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol 2004; 61:727.
  166. Wardle M, Majounie E, Williams NM, et al. Dentatorubral pallidoluysian atrophy in South Wales. J Neurol Neurosurg Psychiatry 2008; 79:804.
  167. Tsuji S. Dentatorubral-pallidoluysian atrophy. Handb Clin Neurol 2012; 103:587.
  168. Gövert F, Schneider SA. Huntington's disease and Huntington's disease-like syndromes: an overview. Curr Opin Neurol 2013; 26:420.
  169. Nagafuchi S, Yanagisawa H, Ohsaki E, et al. Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA). Nat Genet 1994; 8:177.
  170. Yazawa I, Nukina N, Hashida H, et al. Abnormal gene product identified in hereditary dentatorubral-pallidoluysian atrophy (DRPLA) brain. Nat Genet 1995; 10:99.
  171. Igarashi S, Koide R, Shimohata T, et al. Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nat Genet 1998; 18:111.
  172. Ellerby LM, Andrusiak RL, Wellington CL, et al. Cleavage of atrophin-1 at caspase site aspartic acid 109 modulates cytotoxicity. J Biol Chem 1999; 274:8730.
  173. Burke JR, Wingfield MS, Lewis KE, et al. The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nat Genet 1994; 7:521.
  174. Apartis E, Blancher A, Meissner WG, et al. FXTAS: new insights and the need for revised diagnostic criteria. Neurology 2012; 79:1898.
  175. Hagerman R, Hagerman P. Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurol 2013; 12:786.
  176. Oostra BA, Willemsen R. A fragile balance: FMR1 expression levels. Hum Mol Genet 2003; 12 Spec No 2:R249.
  177. Hagerman PJ, Hagerman RJ. Fragile X-associated tremor/ataxia syndrome (FXTAS). Ment Retard Dev Disabil Res Rev 2004; 10:25.
  178. Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet 2004; 74:805.
  179. Brussino A, Gellera C, Saluto A, et al. FMR1 gene premutation is a frequent genetic cause of late-onset sporadic cerebellar ataxia. Neurology 2005; 64:145.
  180. Leehey MA, Berry-Kravis E, Goetz CG, et al. FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology 2008; 70:1397.
  181. Hagerman RJ, Leavitt BR, Farzin F, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004; 74:1051.
  182. Rodriguez-Revenga L, Pagonabarraga J, Gómez-Anson B, et al. Motor and mental dysfunction in mother-daughter transmitted FXTAS. Neurology 2010; 75:1370.
  183. Berry-Kravis E, Potanos K, Weinberg D, et al. Fragile X-associated tremor/ataxia syndrome in sisters related to X-inactivation. Ann Neurol 2005; 57:144.
  184. Hagerman RJ, Leehey M, Heinrichs W, et al. Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 2001; 57:127.
  185. Amiri K, Hagerman RJ, Hagerman PJ. Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. Arch Neurol 2008; 65:19.
  186. Jacquemont S, Hagerman RJ, Leehey M, et al. Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am J Hum Genet 2003; 72:869.
  187. Brunberg JA, Jacquemont S, Hagerman RJ, et al. Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction. AJNR Am J Neuroradiol 2002; 23:1757.
  188. Cohen S, Masyn K, Adams J, et al. Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome. Neurology 2006; 67:1426.
  189. Greco CM, Berman RF, Martin RM, et al. Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). Brain 2006; 129:243.
  190. Hall DA, Berry-Kravis E, Jacquemont S, et al. Initial diagnoses given to persons with the fragile X associated tremor/ataxia syndrome (FXTAS). Neurology 2005; 65:299.
  191. Toft M, Aasly J, Bisceglio G, et al. Parkinsonism, FXTAS, and FMR1 premutations. Mov Disord 2005; 20:230.
  192. Garcia Arocena D, Louis ED, Tassone F, et al. Screen for expanded FMR1 alleles in patients with essential tremor. Mov Disord 2004; 19:930.
  193. Kamm C, Healy DG, Quinn NP, et al. The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group. Brain 2005; 128:1855.
  194. Kamm C, Gasser T. The variable phenotype of FXTAS: a common cause of "idiopathic" disorders. Neurology 2005; 65:190.
  195. Kretzschmar HA, Kufer P, Riethmüller G, et al. Prion protein mutation at codon 102 in an Italian family with Gerstmann-Sträussler-Scheinker syndrome. Neurology 1992; 42:809.
  196. Guerrini L, Lolli F, Ginestroni A, et al. Brainstem neurodegeneration correlates with clinical dysfunction in SCA1 but not in SCA2. A quantitative volumetric, diffusion and proton spectroscopy MR study. Brain 2004; 127:1785.