SCA3: neurological features, pathogenesis and animal models

Cerebellum. 2008;7(2):125-37. doi: 10.1007/s12311-008-0013-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Botulinum Toxins / therapeutic use
  • Brain / pathology
  • Chromosomes, Human, Pair 14*
  • Disease Models, Animal
  • Humans
  • Machado-Joseph Disease / drug therapy
  • Machado-Joseph Disease / genetics*
  • Machado-Joseph Disease / pathology
  • Magnetic Resonance Imaging
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Genetic
  • Trinucleotide Repeat Expansion / genetics
  • Trinucleotide Repeats / genetics


  • Nerve Tissue Proteins
  • Botulinum Toxins