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Brain pathology of spinocerebellar ataxias

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Abstract

The autosomal dominant cerebellar ataxias (ADCAs) represent a heterogeneous group of neurodegenerative diseases with progressive ataxia and cerebellar degeneration. The current classification of this disease group is based on the underlying genetic defects and their typical disease courses. According to this categorization, ADCAs are divided into the spinocerebellar ataxias (SCAs) with a progressive disease course, and the episodic ataxias (EA) with episodic occurrences of ataxia. The prominent disease symptoms of the currently known and genetically defined 31 SCA types result from damage to the cerebellum and interconnected brain grays and are often accompanied by more specific extra-cerebellar symptoms. In the present review, we report the genetic and clinical background of the known SCAs and present the state of neuropathological investigations of brain tissue from SCA patients in the final disease stages. Recent findings show that the brain is commonly seriously affected in the polyglutamine SCAs (i.e. SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) and that the patterns of brain damage in these diseases overlap considerably in patients suffering from advanced disease stages. In the more rarely occurring non-polyglutamine SCAs, post-mortem neuropathological data currently are scanty and investigations have been primarily performed in vivo by means of MRI brain imaging. Only a minority of SCAs exhibit symptoms and degenerative patterns allowing for a clear and unambiguous diagnosis of the disease, e.g. retinal degeneration in SCA7, tau aggregation in SCA11, dentate calcification in SCA20, protein depositions in the Purkinje cell layer in SCA31, azoospermia in SCA32, and neurocutaneous phenotype in SCA34. The disease proteins of polyglutamine ataxias and some non-polyglutamine ataxias aggregate as cytoplasmic or intranuclear inclusions and serve as morphological markers. Although inclusions may impair axonal transport, bind transcription factors, and block protein quality control, detailed molecular and pathogenetic consequences remain to be determined.

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References

  1. Ansorge O, Giunti P, Michalik A et al (2004) Ataxin-7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats. Ann Neurol 56:448–452

    Article  PubMed  CAS  Google Scholar 

  2. Auburger G, Orozco-Diaz GO, Capote RF et al (1990) Autosomal dominant ataxia: genetic evidence for locus heterogeneity from a Cuban founder effect population. Am J Hum Genet 46:1163–1177

    PubMed  CAS  Google Scholar 

  3. Babovic-Vuksanovic D, Snow K, Patterson MC, Michels VV (1998) Spinocerebellar ataxia type 2 (SCA2) in an infant with extreme CAG repeat expansion. Am J Med Genet 12:383–387

    Article  Google Scholar 

  4. Bakalkin G, Watanabe H, Jezierska J et al (2010) Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet 87:593–603

    Article  PubMed  CAS  Google Scholar 

  5. Banfi S, Servadio A, Chung MY et al (1994) Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat Genet 7:513–520

    Article  PubMed  CAS  Google Scholar 

  6. Bauer P, Schöls L, Riess O (2006) Spectrin mutations in spinocerebellar ataxia (SCA). BioEssays 28:785–787

    Article  PubMed  CAS  Google Scholar 

  7. Bauer P, Stevanin G, Beetz C et al (2010) Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds. J Neurol Neurosurg Psychiatry 81:1229–1232

    Article  PubMed  Google Scholar 

  8. Bichelmeier U, Schmidt T, Hübener J et al (2007) Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence. J Neurosci 27:7418–7428

    Article  PubMed  CAS  Google Scholar 

  9. Bouskila M, Esoof N, Gay L et al (2011) TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development. Biochem J 437:157–167

    Article  PubMed  CAS  Google Scholar 

  10. Brkanac Z, Bylenok L, Fernandez M et al (2002) A new dominant spinocerebellar ataxia linked to chromosome 19q13.4-qter. Arch Neurol 59:1291–1295

    Article  PubMed  Google Scholar 

  11. Brkanac Z, Fernandez M, Matsushita M et al (2002) Autosomal dominant sensory/motor neuropathy with ataxia (SMNA): linkage to chromosome 7q22-q32. Am J Med Genet 114:450–457

    Article  PubMed  Google Scholar 

  12. Brkanac Z, Spencer D, Shendure J et al (2009) IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23. Am J Hum Genet 84:692–697

    Article  PubMed  CAS  Google Scholar 

  13. Bruni AC, Takahashi-Fujigasaki J, Maltecca F et al (2004) Behavioural disorder, dementia, ataxia, and rigidity in a large family with TATA box binding protein mutation. Arch Neurol 61:1314–1320

    Article  PubMed  Google Scholar 

  14. Brusse E, de Koning I, Maat-Kievit A, Oostra BA, Heutink P, van Swieten JC (2006) Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): a new phenotype. Mov Disord 21:396–401

    Article  PubMed  Google Scholar 

  15. Bürk K, Abele M, Fetter M et al (1996) Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain 119:1497–1505

    Article  PubMed  Google Scholar 

  16. Bürk K, Fetter M, Abele M et al (1999) Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. J Neurol 246:789–797

    Article  PubMed  Google Scholar 

  17. Bürk K, Globas C, Bösch S et al (2003) Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol 250:207–211

    Article  PubMed  Google Scholar 

  18. Bürk K, Zühlke C, König IR et al (2004) Spinocerebellar ataxia type 5: clinical and molecular genetic features of a German kindred. Neurology 62:327–329

    Article  PubMed  Google Scholar 

  19. Cagnoli C, Mariotti C, Taroni F et al (2006) SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. Brain 129:235–242

    Article  PubMed  Google Scholar 

  20. Cagnoli C, Stevanin G, Brussino A et al (2010) Missense mutations in the AFG3L2 proteolytic domain account for ~1.5% of European autosomal dominant cerebellar ataxias. Hum Mutat 31:1117–1124

    Article  PubMed  CAS  Google Scholar 

  21. Cancel G, Dürr A, Didierjean O et al (1997) Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families. Hum Mol Genet 6:709–715

    Article  PubMed  CAS  Google Scholar 

  22. Cancel GG, Duyckaerts C, Holmberg M et al (2000) Distribution of ataxin-7 in normal human brain and retina. Brain 123:2519–2530

    Article  PubMed  Google Scholar 

  23. Chen DH, Cimono PJ, Ranum LP et al (2005) The clinical and genetic spectrum of spinocerebellar ataxia 14. Neurology 64:1258–1260

    Article  PubMed  CAS  Google Scholar 

  24. Chong SS, MacCall AE, Cota J et al (1995) Gametic and somatic tissue-specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1. Nat Genet 10:344–350

    Article  PubMed  CAS  Google Scholar 

  25. Chung MY, Ly YC, Cheng NC, Soong BW (2003) A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain 126:1293–1299

    Article  PubMed  Google Scholar 

  26. Dalski A, Atici J, Kreuz FR, Hellenbroich Y, Schwinger E, Zühlke C (2005) Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias. Eur J Hum Genet 13:118–120

    Article  PubMed  CAS  Google Scholar 

  27. Daughters RS, Tuttle DL, Gao W et al (2009) RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet 5:e1000600

    Article  PubMed  CAS  Google Scholar 

  28. David G, Abbas N, Stevanin G et al (1997) Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 17:65–70

    Article  PubMed  CAS  Google Scholar 

  29. David G, Dürr A, Stevanin G (1998) Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7). Hum Mol Genet 7:165–170

    Article  PubMed  CAS  Google Scholar 

  30. David G, Giunti P, Abbas N et al (1996) The gene for autosomal dominant cerebellar ataxia type II is located in a 5 cM region in 3p12-13: genetic and physical mapping of the SCA7 locus. Am J Hum Genet 59:1328–1336

    PubMed  CAS  Google Scholar 

  31. Day JW, Schut LJ, Moseley ML, Durand AC, Ranum LP (2000) Spinocerebellar ataxia type 8: clinical features in a large family. Neurology 55:649–657

    Article  PubMed  CAS  Google Scholar 

  32. Delplanque J, Devos D, Vuillaume I et al (2008) Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). Cerebellum 7:179–183

    Article  PubMed  CAS  Google Scholar 

  33. Devos D, Schraen-Maschke S, Vuillaume I et al (2001) Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology 56:234–238

    Article  PubMed  CAS  Google Scholar 

  34. Di Bella D, Lazzaro F, Brusco A et al (2010) Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet 42:313–321

    Article  PubMed  CAS  Google Scholar 

  35. Diener HC, Dichgans J (1992) Pathophysiology of cerebellar ataxia. Mov Disord 7:95–109

    Article  PubMed  CAS  Google Scholar 

  36. do Carmo Costa M, Bajanca F, Rodriguez AJ et al (2010) Ataxin-3 plays a role in the mouse myogenic differentiation through regulation of integrin subunit levels. PLoS ONE 5:e11728

    Article  PubMed  CAS  Google Scholar 

  37. Dudding TE, Friend K, Schofield PW, Lee S, Wilkinson IA, Richards RI (2004) Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. Neurology 63:2288–2292

    Article  PubMed  CAS  Google Scholar 

  38. Dürr A (2010) Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol 9:885–894

    Article  PubMed  CAS  Google Scholar 

  39. Dürr A, Smadja D, Cancel G et al (1995) Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies). Clinical and neuropathological analysis of 53 patients from three unrelated SCA2 families. Brain 118:1573–1581

    Article  PubMed  Google Scholar 

  40. Dürr A, Stevanin G, Cancel G et al (1996) Spinocerebellar ataxia 3 and Machado–Joseph disease: clinical, molecular and neuropathological features. Ann Neurol 39:490–499

    Article  PubMed  Google Scholar 

  41. Duyckearts C, Dürr A, Cancel G, Brice A (1999) Nuclear inclusions in spinocerebellar ataxia type 1. Acta Neuropathol 97:201–207

    Article  Google Scholar 

  42. Edener U, Wöllner J, Hehr U et al (2010) Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation. Eur J Hum Genet 18:965–968

    Article  PubMed  CAS  Google Scholar 

  43. Flanigan K, Gardner K, Alderson K et al (1996) Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Am J Hum Genet 59:392–399

    PubMed  CAS  Google Scholar 

  44. Gao R, Matsuura T, Coolbaugh M et al (2008) Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17. Eur J Hum Genet 16:215–222

    Article  PubMed  CAS  Google Scholar 

  45. Gao Y, Perkins EM, Clarkson YL et al (2011) β-III spectrin is critical for development of purkinje cell dendritic tree and spine morphogenesis. J Neurosci 31:16581–16590

    Article  PubMed  CAS  Google Scholar 

  46. Gardner RJ (2008) “SCA16” is really SCA15. J Med Genet 45:192

    Article  PubMed  CAS  Google Scholar 

  47. Genis D, Matilla T, Volpini V et al (1995) Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms. Neurology 45:24–30

    Article  PubMed  CAS  Google Scholar 

  48. Gierga K, Bürk K, Bauer M et al (2005) Involvement of the cranial nerves and their nuclei in spinocerebellar ataxia type 2 (SCA2). Acta Neuropathol 109:617–631

    Article  PubMed  CAS  Google Scholar 

  49. Gierga K, Scheelhaas HJ, Brunt ER et al (2009) Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites. Neuropathol Appl Neurobiol 35:515–527

    Article  PubMed  CAS  Google Scholar 

  50. Gilman S, Sima AA, Junck L et al (1996) Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions. Ann Neurol 39:241–255

    Article  PubMed  CAS  Google Scholar 

  51. Giroux JM, Barbeau A (1972) Erythrokeratodermia with ataxia. Arch Dermatol 106:183–188

    Article  PubMed  CAS  Google Scholar 

  52. Gispert S, Twells R, Orozco G et al (1993) Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1. Nat Genet 4:295–299

    Article  PubMed  CAS  Google Scholar 

  53. Giunti P, Stevanin G, Worth PF, David G, Brice A, Wood NW (1999) Molecular and clinical study of 18 families with ADCA type II: evidence for genetic heterogeneity and de novo mutation. Am J Hum Genet 64:1594–1603

    Article  PubMed  CAS  Google Scholar 

  54. Gomez CM, Thompson RM, Gammack JT et al (1997) Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset. Ann Neurol 42:933–950

    Article  PubMed  CAS  Google Scholar 

  55. Greenfield JG (1954) The spinocerebellar degenerations. Charles C Thomas, Springfield

  56. Hara K, Shiga A, Nozaki H et al (2008) Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. Neurology 71:547–551

    Article  PubMed  CAS  Google Scholar 

  57. Harding AE (1982) The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the ‘the Drew family of Walworth’. Brain 105:1–28

    Article  PubMed  CAS  Google Scholar 

  58. Hayashi M, Kobayashi K, Furuta H (2005) Immunohistochemical study of neuronal intranuclear and cytoplasmic inclusions in Machado–Joseph disease. Psych Clin Neurosci 57:205–213

    Article  Google Scholar 

  59. Hellenbroich Y, Bernard V, Zühlke C (2008) Spinocerebellar ataxia type 4 and 16q22.1-linked Japanese ataxia are not allelic. J Neurol 255:612–613

    Article  PubMed  CAS  Google Scholar 

  60. Hellenbroich Y, Bubel S, Pawlack H et al (2003) Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region. J Neurol 250:668–671

    Article  PubMed  CAS  Google Scholar 

  61. Hellenbroich Y, Gierga K, Reusche E et al (2006) Spinocerebellar ataxia type 4 (SCA4): initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration. J Neural Transm 113:829–843

    Article  PubMed  CAS  Google Scholar 

  62. Helmlinger D, Hardy S, Abou-Sleymane G et al (2006) Glutamine-expanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol 4:e67

    Article  PubMed  CAS  Google Scholar 

  63. Herman-Bert A, Stevanin G, Netter JC et al (2000) 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 67:229–235

    Article  PubMed  CAS  Google Scholar 

  64. Hernandez A, Magarino C, Gispert S et al (1995) Genetic mapping of the spinocerebellar ataxia 2 (SCA2) locus on chromosome 12q23-q24.1. Genomics 25:433–435

    Article  PubMed  CAS  Google Scholar 

  65. Hoche F, Seidel K, Brunt ER et al (2008) Involvement of the auditory brainstem system in spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7). Neuropathol Appl Neurobiol 34:479–491

    Article  PubMed  CAS  Google Scholar 

  66. Holmberg M, Duyckaerts C, Dürr A et al (1998) Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions. Hum Mol Genet 7:913–918

    Article  PubMed  CAS  Google Scholar 

  67. Holmes G (1907) An attempt to classify cerebellar disease, with a note on Marie’s hereditary cerebellar ataxia. Brain 30:545–567

    Article  Google Scholar 

  68. Holmes SE, O’Hearn E, Margolis RL (2003) Why is SCA12 different from other SCAs? Cytogenet Genome Res 100:189–197

    Article  PubMed  CAS  Google Scholar 

  69. Holmes SE, O’Hearn EE, McInnis MG et al (1999) Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12. Nat Genet 23:391–392

    Article  PubMed  CAS  Google Scholar 

  70. Houlden H, Johnson J, Gardner-Thorpe C et al (2007) Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet 39:1434–1436

    Article  PubMed  CAS  Google Scholar 

  71. Huynh DP, Del Bigio MR, Ho DH, Pulst SM (1999) Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer’s disease and spinocerebellar ataxia 2. Ann Neurol 45:232–241

    Article  PubMed  CAS  Google Scholar 

  72. Ikeda Y, Dick KA, Weatherspoon MR et al (2006) Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet 38:184–190

    Article  PubMed  CAS  Google Scholar 

  73. Imbert G, Saudou F, Yvert G et al (1996) Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 14:285–291

    Article  PubMed  CAS  Google Scholar 

  74. Ishiguro T, Ishikawa K, Takahashi M et al (2010) The carboxy-terminal fragment of alpha(1A) calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells. Acta Neuropathol 119:447–464

    Article  PubMed  CAS  Google Scholar 

  75. Ishikawa K, Watanabe M, Yoshizawa K et al (1999) Clinical, neuropathological, and molecular study in two families with spinocerebellar ataxia type 6 (SCA6). J Neurol Neurosurg Psychiatry 67:86–89

    Article  PubMed  CAS  Google Scholar 

  76. Ito H, Kawakami H, Wate R et al (2006) Clinicopathologic investigation of a family with expanded SCA8 CTA/CTG repeats. Neurology 67:1479–1481

    Article  PubMed  CAS  Google Scholar 

  77. Iwabuchi K, Tsuchiya K, Uchihara T, Yagishita S (1999) Autosomal dominant spinocerebellar degenerations. Clinical, pathological and genetic correlations. Rev Neurol (Paris) 155:255–270

    CAS  Google Scholar 

  78. Jackson JF, Currier RD, Terasaki PI, Morton NE (1977) Spinocerebellar ataxia and HLA linkage: risk prediction by HLA typing. N Engl J Med 296:1138–1141

    Article  PubMed  CAS  Google Scholar 

  79. Jen JC (2008) Hereditary episodic ataxias. Ann N Y Acad Sci 1142:250–253

    Article  PubMed  CAS  Google Scholar 

  80. Jiang H, Zhu HP, Gomez CM (2010) SCA32: an autosomal dominant cerebellar ataxia with azoospermia maps to chromosome 7q32-q33. Mov Disord 25:S192

    Google Scholar 

  81. Kawaguchi Y, Okamoto T, Taniwaki M et al (1994) CAG expansions in a novel gene for Machado–Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228

    Article  PubMed  CAS  Google Scholar 

  82. Klockgether T (2005) Ataxiekrankheiten. Nervenarzt 76:1275–1285

    Article  PubMed  CAS  Google Scholar 

  83. Klockgether T, Paulson H (2011) Milestones in ataxia. Mov Disord 26:1134–1141

    Article  PubMed  Google Scholar 

  84. Knight MA, Gardner RJ, Bahlo M et al (2004) Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain 127:1172–1181

    Article  PubMed  Google Scholar 

  85. Knight MA, Hernandez D, Diede SJ et al (2008) A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20. Hum Mol Genet 17:3847–3853

    Article  PubMed  CAS  Google Scholar 

  86. Kobayashi H, Abe K, Matsuura T et al (2011) Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am J Hum Genet 89:121–130

    Article  PubMed  CAS  Google Scholar 

  87. Koeppen AH (2005) The pathogenesis of spinocerebellar ataxia. Cerebellum 4:62–73

    Article  PubMed  CAS  Google Scholar 

  88. Koide R, Ikeuchi T, Onodera O et al (1994) Unstable expansion of CAG repeat in hereditary dentatorubralpallidoluysian atrophy (DRPLA). Nat Genet 6:9–13

    Article  PubMed  CAS  Google Scholar 

  89. Koide R, Kobayashi S, Shiomohata T et al (1999) A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease? Hum Mol Genet 8:2047–2053

    Article  PubMed  CAS  Google Scholar 

  90. Koob MD, Moseley ML, Schut LJ et al (1999) An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 21:379–384

    Article  PubMed  CAS  Google Scholar 

  91. Koyano S, Uchihara T, Fujigasaki H, Nakamura A, Yagishita S, Iwabuchi K (1999) Neuronal intranuclear inclusions in spinocerebellar ataxia type 2: triple-labeling immunofluorescent study. Neurosci Lett 273:117–120

    Article  PubMed  CAS  Google Scholar 

  92. Lastres-Becker I, Rüb U, Auburger G (2008) Spinocerebellar ataxia 2 (SCA2). Cerebellum 7:115–124

    Article  PubMed  CAS  Google Scholar 

  93. Lebre AS, Brice A (2003) Spinocerebellar ataxia 7 (SCA7). Cytogenet Genome Res 100:154–163

    Article  PubMed  CAS  Google Scholar 

  94. Li SH, Margolis RL, Ross CA (1994) Expression of mRNA for DRPLA gene (atrophin-1) and HD gene (IT15) in developmental and adult brain. Neurosci Abstr 24:1648

    Google Scholar 

  95. Lin JX, Ishikawa K, Sakamoto M et al (2008) Direct and accurate measurement of CAG repeat configuration in the ataxin-1 (ATXN-1) gene by “dual-fluorescence labeled PCR-restriction fragment length analysis”. J Hum Genet 53:287–295

    Article  PubMed  CAS  Google Scholar 

  96. Lindblad K, Savontaus ML, Stevanin G et al (1996) An expanded CAG repeat sequence in spinocerebellar ataxia type 7. Genome Res 6:965–971

    Article  PubMed  CAS  Google Scholar 

  97. Liu G, Bissler JJ, Sinden RR, Leffak M (2007) Unstable spinocerebellar ataxia type 10 (ATTCT*(AGAAT) repeats are associated with aberrant replication at the ATX10 locus and replication-origin dependent expansion at an ectopic site in human cells. Mol Cell Biol 27:7828–7838

    Article  PubMed  CAS  Google Scholar 

  98. Lukas C, Hahn HK, Bellenberg B et al (2008) Spinal cord atrophy in spinocerebellar ataxia type 3 and 6: impact on clinical disability. J Neurol 255:1244–1249

    Article  PubMed  Google Scholar 

  99. Manto M, Marmolino D (2009) Cerebellar ataxias. Curr Opin Neurol 22:419–429

    Article  PubMed  Google Scholar 

  100. Mantuano E, Veneziano L, Jodice C, Frontali M (2003) Spinocerebellar ataxia type 6 and episodic ataxia type 2: differences and similarities between two allelic disorders. Cytogenet Genome Res 1000:147–153

    Article  CAS  Google Scholar 

  101. Marelli C, van de Leemput J, Johnson JO et al (2011) SCA15 due to large ITPR1 deletions in a cohort of 333 white families with dominant ataxia. Arch Neurol 68:637–643

    Article  PubMed  Google Scholar 

  102. Marie P (1893) Sur l’hérédoataxie cérébelleuse. Semaines de Medicine, Paris 13:444–447

    Google Scholar 

  103. Matsuura T, Yamagata T, Burgess DL et al (2000) Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 26:191–194

    Article  PubMed  CAS  Google Scholar 

  104. Mauger C, Del Favero J, Ceuterick C, Lübke U, van Broeckhoven C, Martin J (1999) Identification and localization of ataxin-7 in brain and retina of a patient with cerebellar ataxia type II using anti-peptide antibody. Brain Res Mol Brain Res 74:35–43

    Article  PubMed  CAS  Google Scholar 

  105. Michalik A, Martin JJ, van Broeckhoven C (2004) Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy. Eur J Hum Genet 12:2–15

    Article  PubMed  CAS  Google Scholar 

  106. Morton SM, Bastian AJ (2004) Cerebellar control of balance and locomotion. Neuroscientist 10:247–259

    Article  PubMed  Google Scholar 

  107. Moseley ML, Zu T, Ikeda Y et al (2006) Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet 38:758–769

    Article  PubMed  CAS  Google Scholar 

  108. Nagaoka U, Takashima M, Ishikawa K et al (2000) A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia. Neurology 54:1971–1975

    Article  PubMed  CAS  Google Scholar 

  109. Nagaoka U, Uchihara T, Iwabuchi K et al (2003) Attenuated nuclear shrinkage in neurones with nuclear inclusions of SCA1 brains. J Neurol Neurosurg Psychiatry 74:597–601

    Article  PubMed  CAS  Google Scholar 

  110. Nakamura K, Jeong SY, Uchihara T et al (2001) SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 10:1441–1448

    Article  PubMed  CAS  Google Scholar 

  111. Nemes JP, Benzow KA, Moseley ML, Ranum LP, Koob MD (2000) The SCA8 transcript is an antisense RNA to a brain-specific transcript encoding a novel actin-binding protein (KLHL1). Hum Mol Genet 12:1543–1551

    Article  Google Scholar 

  112. O’Hearn E, Holmes SE, Calvert PC, Ross CA, Margolis RL (2001) SCA-12: tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion. Neurology 56:299–303

    Article  PubMed  Google Scholar 

  113. O’Hearn E, Holmes SE, Margolis RL (2012) Spinocerebellar ataxia type 12. Handb Clin Neurol 103:535–547

    Article  PubMed  Google Scholar 

  114. Orozco G, Estrada R, Perry TL et al (1989) Dominantly inherited olivopontocerebellar atrophy from eastern Cuba. Clinical, neuropathological, and biochemical findings. J Neurol Sci 93:37–50

    Article  PubMed  CAS  Google Scholar 

  115. Orr HT (2000) The ins and outs of a polyglutamine neurodegenerative disease: spinocerebellar ataxia type 1 (SCA1). Neurobiol Dis 7:129–134

    Article  PubMed  CAS  Google Scholar 

  116. Orr HT, Chung MY, Banfi S et al (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 4:221–226

    Article  PubMed  CAS  Google Scholar 

  117. Orr HT, Zoghbi HY (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575–621

    Article  PubMed  CAS  Google Scholar 

  118. Owada K, Ishikawa K, Toru S et al (2005) A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III. Neurology 65:629–632

    Article  PubMed  CAS  Google Scholar 

  119. Pang JT, Giunti P, Chamberlain S et al (2002) Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases. Brain 125:656–663

    Article  PubMed  Google Scholar 

  120. Paulson H (2009) The spinocerebellar ataxias. J Neuroophthalmol 29:227–237

    Article  PubMed  Google Scholar 

  121. Paulson H, Ammache Z (2001) Ataxia and hereditary disorders. Neurol Clin 19:759–782

    Article  PubMed  CAS  Google Scholar 

  122. Paulson HL, Perez MK, Trottier Y et al (1997) Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron 19:333–344

    Article  PubMed  CAS  Google Scholar 

  123. Pulst SM, Nechiporuk A, Nechiporuk T et al (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet 14:269–276

    Article  PubMed  CAS  Google Scholar 

  124. Ramos EM, Martins S, Alonso I et al (2010) Common origin of pure and interrupted repeat expansions in spinocerebellar ataxia type 2 (SCA2). Am J Med Genet B Neuropsychiatr Genet 153B:524–531

    PubMed  CAS  Google Scholar 

  125. Ranum LP, Schut LJ, Lundgren JK, Orr HT, Livingston DM (1994) Spinocerebellar ataxia type 5 in a family descended from the grandparents of president Lincoln maps to chromosome 11. Nat Genet 8:280–284

    Article  PubMed  CAS  Google Scholar 

  126. Rasmussen A, Matsuura T, Ruano L et al (2001) Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol 50:234–239

    Article  PubMed  CAS  Google Scholar 

  127. Riess O, Laccone FA, Gispert S et al (1997) SCA2 trinucleotide expansion in German SCA patients. Neurogenetics 2:59–64

    Article  Google Scholar 

  128. Riess O, Rüb U, Pastore A, Bauer P, Schöls L (2008) SCA3: neurological features, pathogenesis and animal models. Cerebellum 7:125–137

    Article  PubMed  CAS  Google Scholar 

  129. Riess O, Schöls L, Bottger H et al (1997) SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene. Hum Mol Genet 6:1289–1293

    Article  PubMed  CAS  Google Scholar 

  130. Robitaille Y, Lopes-Cendes I, Becher M, Rouleau G, Clark AW (1997) The neuropathology of CAG repeat diseases: review and update of genetic and molecular features. Brain Pathol 7:901–926

    Article  PubMed  CAS  Google Scholar 

  131. Robitaille Y, Schut L, Kish SJ (1995) Structural and immunocytochemical features of olivopontocerebellar atrophy caused by the spinocerebellar ataxia type 1 (SCA-1) mutation define a unique phenotype. Acta Neuropathol 90:572–581

    Article  PubMed  CAS  Google Scholar 

  132. Rolfs A, Koeppen AH, Bauer I et al (2003) Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). Ann Neurol 54:367–375

    Article  PubMed  Google Scholar 

  133. Rosenberg RN (1995) Autosomal dominant cerebellar phenotypes: the genotype has settled the issue. Neurology 45:1–5

    Article  PubMed  CAS  Google Scholar 

  134. Rüb U, Brunt ER, de Vos RA et al (2004) Degeneration of the central vestibular system in spinocerebellar ataxia type 3 (SCA3) patients and its possible clinical significance. Neuropathol Appl Neurobiol 30:402–414

    Article  PubMed  Google Scholar 

  135. Rüb U, Brunt ER, Gierga K et al (2003) The nucleus raphe interpositus in spinocerebellar ataxia type 3 (Machado Joseph disease). J Chem Neuroanat 25:115–127

    Article  PubMed  CAS  Google Scholar 

  136. Rüb U, Brunt ER, Gierga K et al (2005) Spinocerebellar ataxia type 7 (SCA7): first report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat. Brain Pathol 15:287–295

    Article  PubMed  Google Scholar 

  137. Rüb U, Brunt ER, Petrasch-Parwez E et al (2006) Degeneration of ingestion related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7. Neuropathol Appl Neurobiol 32:635–649

    Article  PubMed  Google Scholar 

  138. Rüb U, Bürk K, Schöls L et al (2004) Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2 and 3. Neurology 63:1258–1263

    Article  PubMed  Google Scholar 

  139. Rüb U, Bürk K, Timmann D et al (2012) Spinocebellar ataxia type 1 (SCA1): new pathoanatomical and clinico-pathological insights. Neuropathol Appl Neurobiol. doi:10.1111/j.1365-2990.2012.01259.x

  140. Rüb U, de Vos RA, Brunt ER et al (2006) Spinocerebellar ataxia type 3 (SCA3): thalamic neurodegeneration occurs independently from thalamic ataxin-3 immunopositive neuronal intranuclear inclusions. Brain Pathol 16:218–227

    Article  PubMed  Google Scholar 

  141. Rüb U, de Vos RA, Schultz C, Brunt ER, Paulson H, Braak H (2002) Spinocerebellar ataxia type 3 (Machado–Joseph disease): severe destruction of the lateral reticular nucleus. Brain 125:2115–2124

    Article  PubMed  Google Scholar 

  142. Rüb U, Del Turco D, Bürk K et al (2005) Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2. Neuropathol Appl Neurobiol 31:127–140

    Article  PubMed  Google Scholar 

  143. Rüb U, Turco Del, Del Tredici K et al (2003) Thalamic involvement in a spinocerebellar ataxia type 2 (SCA2) and a spinocerebellar type 3 (SCA3) patient, and its clinical relevance. Brain 126:2257–2272

    Article  PubMed  Google Scholar 

  144. Rüb U, Gierga K, Brunt ER et al (2005) Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum. J Neural Transm 112:1523–1545

    Article  PubMed  Google Scholar 

  145. Rüb U, Seidel K, Ozerden I et al (2007) Consistent affection of the central somatosensory system in spinocerebellar ataxia type 2 and type 3 and its significance for clinical symptoms and rehabilitative therapy. Brain Res Rev 53:235–249

    Article  PubMed  CAS  Google Scholar 

  146. Rujano MA, Bosveld F, Salomons FA et al (2006) Polarised asymmetric inheritance of accumulated protein damage in higher eukaryotes. PLoS Biol 4:e417

    Article  PubMed  CAS  Google Scholar 

  147. Sakai H, Yoshida K, Shimizu Y, Morita H, Ikeda S, Matsumoto N (2010) Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan. Neurogenetics 11:409–415

    Article  PubMed  CAS  Google Scholar 

  148. Sanpei K, Takano H, Igarashi S et al (1996) Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet 14:277–284

    Article  PubMed  CAS  Google Scholar 

  149. Sasaki H, Yabe I, Tashiro K (2003) The hereditary spinocerebellar ataxias in Japan. Cytogenet Genome Res 100:198–205

    Article  PubMed  CAS  Google Scholar 

  150. Sato N, Amino T, Kobayashi K et al (2009) Spinocerebellar ataxia type 31 is associated with “inserted” penta-nucleotide repeats containing (TGGAA)n. Am J Hum Genet 85:544–557

    Article  PubMed  CAS  Google Scholar 

  151. Schelhaas HJ, Ippel PF, Hageman G, Sinke RJ, van der Laan EN, Beemer HA (2001) Clinical and genetic analysis of a four-generation family with a distinct autosomal cerebellar ataxia. J Neurol 248:113–120

    Article  PubMed  CAS  Google Scholar 

  152. Schelhaas HJ, Verbeek DS, van de Warrenburg BP, Sinke RJ (2004) SCA19 and SCA22: evidence for one locus with a worldwide distribution. Brain 127:E6

    Article  PubMed  Google Scholar 

  153. Schmidt T, Landwehrmeyer GB, Schmitt I et al (1998) An isoform of ataxin-3 accumulates in the nucleus of neuronal cells in affected brain regions of SCA3 patients. Brain Pathol 8:669–679

    Article  PubMed  CAS  Google Scholar 

  154. Schöls L, Bauer P, Schmidt T, Schulte T, Riess O (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3:291–304

    Article  PubMed  Google Scholar 

  155. Schöls L, Gispert S, Vorgerd M et al (1997) Spinocerebellar ataxia type 2. Genotype and phenotype in German kindreds. Arch Neurol 54:1073–1080

    Article  PubMed  Google Scholar 

  156. Schöls L, Krüger R, Amoiridis G et al (1998) Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds. J Neurol Neurosurg Psychiatry 64:67–73

    Article  PubMed  Google Scholar 

  157. Schöls L, Riess O, Schöls S et al (1995) Spinocerebellar ataxia type 1: clinical and neurophysiological characteristics in German kindreds. Acta Neurol Scand 92:478–485

    Article  PubMed  Google Scholar 

  158. Seidel K, Brunt ER, de Vos RA (2009) The p62 antibody reveals various cytoplasmic protein aggregates in spinocerebellar ataxia type 6. Clin Neuropathol 28:344–349

    PubMed  CAS  Google Scholar 

  159. Seidel K, den Dunnen WF, Schultz C et al (2010) Axonal inclusions in spinocerebellar ataxia type 3. Acta Neuropathol 120:449–460

    Article  PubMed  CAS  Google Scholar 

  160. Seidel K, Meister M, Dugbartey GJ et al (2011) Cellular protein quality control and the evolution of aggregates in SCA3. Neuropathol Appl Neurobiol. doi:10.1111/j.1365-2990.2011.01220.x

  161. Seki T, Shimahara T, Yamamoto K et al (2009) Mutant gammaPKC found in spinocerebellar ataxia type 14 induces aggregate-independent maldevelopment of dendrites in primary cultured Purkinje cells. Neurobiol Dis 33:260–273

    Article  PubMed  CAS  Google Scholar 

  162. Skinner PJ, Koshy BT, Cummings CJ et al (1997) Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature 389:971–974

    Article  PubMed  CAS  Google Scholar 

  163. Soong BW, Paulson HL (2007) Spinocerebellar ataxias: an update. Curr Opin Neurol 20:438–446

    Article  PubMed  CAS  Google Scholar 

  164. Stevanin G, Bouslam N, Thobois S et al (2004) Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. Ann Neurol 55:97–104

    Article  PubMed  CAS  Google Scholar 

  165. Storey E (1998) Dominantly inherited ataxias. Part I. J Clin Neurosci 5:257–264

    Article  PubMed  CAS  Google Scholar 

  166. Storey E, Bahlo M, Fahey M et al (2009) A new dominantly inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry 80:408–411

    Article  PubMed  CAS  Google Scholar 

  167. Storey E, Gardner RJ, Knight MA et al (2001) A new autosomal dominant pure cerebellar ataxia. Neurology 57:1913–1915

    Article  PubMed  CAS  Google Scholar 

  168. Takahashi H, Hayashi Sato T (2002) A 76-year-old woman presenting with adult-onset, slowly progressive cerebellar symptoms. Neuropathology 22:360–361

    Article  PubMed  Google Scholar 

  169. Takahashi H, Yamada M, Tsuji S (2003) Dentatorubral-pallidoluysian Atrophy. In: Dickson D (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 269–274

    Google Scholar 

  170. Teive HA, Munoz RP, Raskin S et al (2010) Spinocerebellar ataxia type 10: frequency of epilepsy in a large sample of Brazilian patients. Mov Disord 25:2875–2878

    Article  PubMed  Google Scholar 

  171. Tong X, Gui H, Jin F et al (2011) Ataxin-1 and Brother of ataxin-1 are components of the Notch signalling pathway. EMBO Rep 12:428–435

    Article  PubMed  CAS  Google Scholar 

  172. Toyoshima Y, Tanaka H, Shimohata M et al (2011) Spinocerebellar ataxia type 2 (SCA2) is associated with TDP-43 pathology. Acta Neuropathol 122:375–378

    Article  PubMed  Google Scholar 

  173. Trottier Y, Lutz Y, Stevanin G et al (1995) Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 378:403–406

    Article  PubMed  CAS  Google Scholar 

  174. Tsunemi T, Ishikawa K, Jin H, Mizusawa H (2008) Cell-type-specific alternative splicing in spinocerebellar ataxia type 6. Neurosci Lett 447:78–81

    Article  PubMed  CAS  Google Scholar 

  175. Uchihara T, Iwabuchi K, Funata N, Yagashita S (2002) Attenuated nuclear shrinkage in neurons with nuclear aggregates—a morphometric study on pontine neurons of Machado–Joseph disease brains. Exp Neurol 178:124–128

    Article  PubMed  Google Scholar 

  176. van de Leemput J, Wavrant-De Vrièze F, Rafferty I et al (2010) Sequencing analysis of the ITPR1 gene in a pure autosomal dominant spinocerebellar ataxia series. Mov Disord 25:771–773

    Article  PubMed  Google Scholar 

  177. van Roon-Mom WM, Reid JJ, Faull RL, Snell RG (2005) TATA-binding protein in neurodegenerative disease. Neuroscience 133:863–872

    Article  PubMed  CAS  Google Scholar 

  178. Van Swieten JC, Brusse E, de Graaf BM et al (2003) A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia. Am J Hum Genet 72:191–199

    Article  PubMed  Google Scholar 

  179. Verbeek DS, Goedhart J, Bruinsma L, Sinke RJ, Reits EA (2008) PKC gamma mutations in spinocerebellar ataxia type 14 affect C1 domain accessibility and kinase activity leading to aberrant MAPK signalling. J Cell Sci 121:2339–2349

    Article  PubMed  CAS  Google Scholar 

  180. Verbeek DS, Schelhaas JH, Ippel EF, Beemer FA, Pearson PL, Sinke RJ (2002) Identification of a novel SCA locus (SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Hum Genet 111:388–393

    Article  PubMed  CAS  Google Scholar 

  181. Verbeek DS, van de Warrenburg BP, Wesseling P, Pearson PL, Kremer HP, Sinke RJ (2004) Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain 127:2551–2557

    Article  PubMed  CAS  Google Scholar 

  182. Vlak MH, Sinke RJ, Rabelink GM, Kremer BP, van de Warrenburg BP (2006) Novel PRKCG/SCA14 mutation in a Dutch spinocerebellar ataxia family: expanding the phenotype. Mov Disord 21:1025–1028

    Article  PubMed  Google Scholar 

  183. Vuillaume I, Devos D, Schraen-Maschke S et al (2002) A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. Ann Neurol 52:666–670

    Article  PubMed  CAS  Google Scholar 

  184. Wang JL, Yang X, Xia K et al (2010) TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 133:3510–3518

    Article  PubMed  Google Scholar 

  185. Wang Q, Bardgett ME, Wong M et al (2002) Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14. Neuron 35:25–38

    Article  PubMed  CAS  Google Scholar 

  186. Waters MF, Minassian NA, Stevanin G et al (2006) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 38:447–451

    Article  PubMed  CAS  Google Scholar 

  187. Williams AJ, Paulson HL (2008) Polyglutamine neurodegeneration: protein misfolding revisited. Trends Neurosci 31:521–528

    Article  PubMed  CAS  Google Scholar 

  188. Winborn BJ, Travis SM, Todi SV et al (2008) The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains. J Biol Chem 283:26436–26443

    Article  PubMed  CAS  Google Scholar 

  189. Worth PF, Giunti P, Gardner-Thorpe C, Dixon PH, Davis MB, Wood NW (1999) 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 65:420–426

    Article  PubMed  CAS  Google Scholar 

  190. Yabe I, Sasaki H, Chen DH (2003) Spinocerebellar ataxia type 14 caused by a mutation in protein kinase C gamma. Arch Neurol 60:1749–1751

    Article  PubMed  Google Scholar 

  191. Yakura H, Wakisaka A, Fujimoto S, Itakura K (1974) Letter: hereditary ataxia and HL-A. N Engl J Med 291:154–155

    PubMed  CAS  Google Scholar 

  192. Yamada M (2010) Dentatorubral-pallidoluysian atrophy. Neuropathology 30:453–457

    Google Scholar 

  193. Yamada M, Sato T, Tsuji S, Takashi H (2008) CAG repeat disorder models and human neuropathology: similarities and differences. Acta Neuropathol 115:71–86

    Article  PubMed  CAS  Google Scholar 

  194. Yamanaka T, Nukina N (2010) Transcription factor sequestration by polyglutamine proteins. Methods Mol Biol 648:215–229

    Article  PubMed  CAS  Google Scholar 

  195. Yamashita I, Sasaki H, Yabe I et al (2000) 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 48:156–163

    Article  PubMed  CAS  Google Scholar 

  196. Yu GY, Howell MJ, Roller MJ, Xie TD, Gomez CM (2005) Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol 57:349–354

    Article  PubMed  CAS  Google Scholar 

  197. Zoghbi HY, Orr HT (2000) Glutamine repeats and neurodegeneration. Annu Rev Neurosci 23:217–247

    Article  PubMed  CAS  Google Scholar 

  198. Zu L, Figueroa KP, Grewal R, Pulst SM (1999) Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet 64:594–599

    Article  PubMed  CAS  Google Scholar 

  199. Zuchenko O, Bailey J, Bonnen P (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 15:62–69

    Article  Google Scholar 

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Acknowledgments

Supported by grants from the ADCA-Vereniging Nederland, the Stiftung Hoffnung (Köln, Germany), the Deutsche Heredo-Ataxie Gesellschaft (DHAG) and the Dr. Senckenbergische Stiftung (Frankfurt/Main, Germany). The skilful assistance of I. Szasz (graphics) and M. Bouzrou (immunohistochemistry) is thankfully acknowledged.

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  1. Dr. Senckenbergisches Chronomedizinisches Institut, Goethe University, Theodor-Stern-Kai 7, 60950, Frankfurt/Main, Germany

    Kay Seidel, Sonny Siswanto, Horst-Werner Korf & Udo Rüb

  2. Department of Neurology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Ewout R. P. Brunt

  3. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9700 RB, Groningen, The Netherlands

    Wilfred den Dunnen

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Seidel, K., Siswanto, S., Brunt, E.R.P. et al. Brain pathology of spinocerebellar ataxias. Acta Neuropathol 124, 1–21 (2012). https://doi.org/10.1007/s00401-012-1000-x

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