The Cerebellum

, Volume 7, Issue 2, pp 125–137 | Cite as

SCA3: Neurological features, pathogenesis and animal models

  • Olaf RiessEmail author
  • Udo Rüb
  • Annalisa Pastore
  • Peter Bauer
  • Ludger Schöls
Original Article


The most frequent subtype of autosomal dominant inherited spinocerebellar ataxias is caused by CAG repeat expansions of more than 55 units in the ataxin-3 gene. The clinical variability of the phenotype depends on the length of the expanded repeat and the age at onset (and thus indirectly with the repeat size). Anticipation of the phenotype is most frequently associated with repeat expansions in paternal transmission. In this review we describe four clinical subphenotypes and correlate them to the respective repeat expansions. We also provide a detailed description of the neuropathological features. Finally, we discuss the current knowledge on the function of normal and dysfunction of altered ataxin-3 and how this translates to the predicted structure of the protein.

Key words

Spinocerebellar ataxia 3 Machado-Joseph disease ataxin 3 polyglutamine disease mosaicism 


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Olaf Riess
    • 1
    Email author
  • Udo Rüb
    • 2
  • Annalisa Pastore
    • 3
  • Peter Bauer
    • 1
  • Ludger Schöls
    • 4
  1. 1.Department of Medical GeneticsUniversity of TuebingenTuebingenGermany
  2. 2.Department of Clinical NeuroanatomyJohann Wolfgang Goethe University Frankfurt/Main Germany
  3. 3.National Institute for Medical ResearchLondonUK
  4. 4.Center of Neurology and Hertie-Institute for Clinical Brain ResearchUniversity of TuebingenTuebingenGermany

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