Parkinsonism & Related Disorders
Volume 15, Issue 9 , Pages 621-626 , 5 November 2009

Spinocerebellar ataxia 8: Variable phenotype and unique pathogenesis

  • Amitabh Gupta

      Affiliations

    • Department of Neurology, University of Toronto, Toronto, ON, Canada M5T 2S8
  • ,
  • Joseph Jankovic

      Affiliations

    • Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
    • Corresponding Author InformationCorresponding author. Parkinson's Disease Center, and Movement Disorders Clinic, Baylor College of Medicine, Department of Neurology, the Smith Tower, Suite 1801, 6550 Fannin, Houston, Texas 77030, US. Tel.: +1 713 798 5998, appointments: +1 713 798 7438; fax: +1 713 798 6808.
    web address

Received 9 January 2009 ,Revised 1 June 2009 ,Accepted 2 June 2009.

References 

  1. Koob MD, Moseley ML, Schut LJ, Benzow KA, Bird TD, Day JW, et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet. 1999;21:379–384
  2. Mutsuddi M, Rebay I. Molecular genetics of spinocerebellar ataxia type 8 (SCA8). RNA Biol. 2005;2:49–52
  3. Paulson HL. If it's not one thing, it's another. Nat Genet. 2006;38:743–744
  4. Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters RS, et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet. 2006;38:758–769
  5. Moseley ML, Weatherspoon M, Rasmussen L, Day JW, Ranum LP. SCA8 BAC transgenic mice have a progressive and lethal neurological phenotype demonstrating pathogenicity of the CTG expansion. Am J Hum Genet. 2002;71:A176
  6. Mutsuddi M, Marshall CM, Benzow KA, Koob MD, Rebay I. The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and associates with staufen in Drosophila. Curr Biol. 2004;14:302–308
  7. Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005;4:2–6
  8. Soong BW, Paulson HL. Spinocerebellar ataxias: an update. Curr Opin Neurol. 2007;20:438–446
  9. Mosemiller AK, Dalton JC, Day JW, Ranum LP. Molecular genetics of spinocerebellar ataxia type 8 (SCA8). Cytogenet Genome Res. 2003;100:175–183
  10. Silveira I, Alonso I, Guimarães L, Mendonça P, Santos C, Maciel P, et al. High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles. Am J Hum Genet. 2000;66:830–840
  11. Zeman A, Stone J, Porteous M, Burns E, Barron L, Warner J. Spinocerebellar ataxia type 8 in Scotland: genetic and clinical features in seven unrelated cases and a review of published reports. J Neurol Neurosurg Psychiatry. 2004;75:459–465
  12. Torrens L, Burns E, Stone J, Graham C, Wright H, Summers D, et al. Spinocerebellar ataxia type 8 in Scotland: frequency, neurological, neuropsychological and neuropsychiatric findings. Acta Neurol Scand. 2008;117:41–48
  13. Vincent JB, Neves-Pereira ML, Paterson AD, Yamamoto E, Parikh AV, Macciardi F, et al. An unstable trinucleotide-repeat region on chromosome 13 implicated in spinocerebellar ataxia: a common expansion locus. Am J Hum Genet. 2000;66:819–829
  14. Vincent JB, Yuan Q-P, Schalling M, Adolfsson R, Azevedo MH, Macedo A, et al. Long repeat tracts at SCA8 in major psychosis. Am J Med Genet. 2000;96:873–876
  15. Schöls L, Bauer I, Zuhlke C, Schulte T, Kölmel C, Burk K, et al. Do CTG expansions at the SCA8 locus cause ataxia?. Ann Neurol. 2003;54:110–115
  16. Topisirovic I, Dragasevic N, Savic D, Ristic A, Keckarevic M, Keckarevic D, et al. Genetic and clinical analysis of spinocerebellar ataxia 8 repeat expansion in Yugoslavia. Clin Genet. 2002;62:321–324
  17. Moseley ML, Schut LJ, Bird TD, Koob MD, Day JW, Ranum LP. SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance. Hum Mol Genet. 2000;9:2125–2130
  18. Ikeda Y, Daughters RS, Ranum LP. Bidirectional expression of the SCA8 expansion mutation: one mutation, two genes. Cerebellum. 2008;7:150–158
  19. Maschke M, Oehlert G, Xie TD, Perlman S, Subramony SH, Kumar N, et al. Clinical feature profile of spinocerebellar ataxia type 1–8 predicts genetically defined subtypes. Mov Disord. 2005;20:1405–1412
  20. Baba Y, Uitti RJ, Farrer MJ, Wszolek ZK. Sporadic SCA8 mutation resembling corticobasal degeneration. Parkinsonism Relat Disord. 2005;11:147–150
  21. Day JW, Schut LJ, Moseley ML, Durand AC, Ranum LP. Spinocerebellar ataxia type 8: clinical features in a large family. Neurology. 2000;55:649–657
  22. Ikeda Y, Shizuka M, Watanabe M, Okamoto K, Shoji M. Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan. Neurology. 2000;54:950–955
  23. Juvonen V, Hietala M, Päivärinta M, Rantamäki M, Hakamies L, Kaakkola S, et al. Clinical and genetic findings in Finnish ataxia patients with the spinocerebellar ataxia 8 repeat expansion. Ann Neurol. 2000;48:354–361
  24. Jardim LB, Silveira I, Pereira ML. A survey of spinocerebellar ataxia in South Brasil – 66 new cases with Machado-Joseph disease, SCA7, SCA8, or unidentified disease-causing mutations. J Neurol. 2001;248:870–876
  25. Sempere AP, Millan JM, Royo-Vilanova C, Medrano V. Type 8 spinocerebellar ataxia. A report of a family. Rev Neurol. 2001;33:150–152
  26. Brusco A, Cagnoli C, Franco A, Dragone E, Nardacchione A, Grosso E, et al. Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions. J Neurol. 2002;249:923–929
  27. Tazon B, Badenas C, Jiminez L, Munoz E, Mila M. SCA8 in the Spanish population including one homozygous patient. Clin Genet. 2002;62:404–409
  28. Izumi Y, Maruyama H, Oda M, Morino H, Okada T, Ito H, et al. SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6. Am J Hum Genet. 2003;72:704–709
  29. Felling RJ, Barron TF. Early onset of ataxia in a child with a pathogenic SCA8 allele. Pediatr Neurol. 2005;33:136–138
  30. Kenney C, Diamond A, Mejia N, Davidson A, Hunter C, Jankovic J. Distinguishing psychogenic and essential tremor. J Neurol Sci. 2007;263:94–99
  31. Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW, et al. Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain. 2007;130:2484–2493
  32. Blakeley J, Jankovic J. Secondary paroxysmal dyskinesias. Mov Disord. 2002;17:726–734
  33. Sulek A, Hoffman-Zacharska D, Zdzienicka E, Zaremba J. SCA8 repeat expansion coexists with SCA1–not only with SCA6. Am J Hum Genet. 2003;73:972–974
  34. Factor SA, Qian J, Lava NS, Hubbard JD, Payami H. False-positive SCA8 gene test in a patient with pathologically proven multiple system atrophy. Ann Neurol. 2005;57:462–463
  35. Wu YR, Lin HY, Chen CM, Gwinn-Hardy K, Ro LS, Wang YC, et al. Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease. Clin Genet. 2004;65:209–214
  36. Sobrido MJ, Cholfin JA, Perlman S, Pulst SM, Geschwind DH. SCA8 repeat expansions in ataxia: a controversial association. Neurology. 2001;57:1310–1312
  37. Ikeda Y, Dalton JC, Moseley ML, Gardner KL, Bird TD, Ashizawa T, et al. Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia. Am J Hum Genet. 2004;75:3–16
  38. Kenney C, Powell S, Jankovic J. Autopsy-proven Huntington's disease with 29 trinucleotide repeats. Mov Disord. 2007;22:127–130
  39. Worth PF, Houlden H, Giunti P, Davis MB, Wod NW. Large, expanded repeats in SCA8 are not confined to patients with cerebellar ataxia. Nat Genet. 2000;24:214–215
  40. Lee YC, Liu CS, Wu HM, Wang PS, Chang MH, Soong BW. The 'hot cross bun' sign in the patients with spinocerebellar ataxia. Eur J Neurol. 2009 Apr;16(4):513–516
  41. Kumar N, Miller GM. White matter hyperintense lesions in genetically proven spinocerebellar ataxia 8. Clin Neurol Neurosurg. 2008;110(1):65–68
  42. Ito H, Kawakami H, Wate R, Matsumoto S, Imai T, Hirano A, et al. Clinicopathologic investigation of a family with expanded SCA8 CTA/CTG repeats. Neurology. 2006;67:1479–1481
  43. Lilja A, Hämäläinen P, Kaitaranta E, Rinne R. Cognitive impairment in spinocerebellar ataxia type 8. J Neurol Sci. 2005;237:31–38
  44. Chen WL, Lin JW, Huang HJ, Wang SM, Su MT, Lee-Chen GJ, et al. Sca8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to SCA8 pathology. Brain Res. 2008;1233:176–184
  45. Nemes JP, Benzow KA, Moseley ML, Ranum LP, Koob MD. The SCA8 transcript is an antisense RNA to a brain-specific transcript encoding a novel actin-binding protein (KLHL1). Hum Mol Genet. 2000;9:1543–1551
  46. He Y, Zu T, Benzow KA, Orr HT, Clark HB, Koob MD. Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits. J Neurosci. 2006;26:9975–9982
  47. Aromolaran KA, Benzow KA, Koob MD, Piedras-Renteria ES. The Kelch-like protein 1 modulates P/Q-type calcium current density. Neuroscience. 2007;145:841–850
  48. Vincent M, Hadjikhani N. The cerebellum and migraine. Headache. 2007;47:820–833

 The review of this paper was entirely handled by the Co-Editor-in-Chief, Z.K. Wszolek.

PII: S1353-8020(09)00143-6

doi: 10.1016/j.parkreldis.2009.06.001

Parkinsonism & Related Disorders
Volume 15, Issue 9 , Pages 621-626 , 5 November 2009