Original Article

The Cerebellum

, Volume 7, Issue 2, pp 125-137

First online:

SCA3: Neurological features, pathogenesis and animal models

  • Olaf RiessAffiliated withDepartment of Medical Genetics, University of Tuebingen Email author 
  • , Udo RübAffiliated withDepartment of Clinical Neuroanatomy, Johann Wolfgang Goethe University Frankfurt/Main
  • , Annalisa PastoreAffiliated withNational Institute for Medical Research
  • , Peter BauerAffiliated withDepartment of Medical Genetics, University of Tuebingen
  • , Ludger SchölsAffiliated withCenter of Neurology and Hertie-Institute for Clinical Brain Research, University of Tuebingen

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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