Recent advances in the genetics of cerebellar ataxias

Curr Neurol Neurosci Rep. 2012 Jun;12(3):227-36. doi: 10.1007/s11910-012-0267-6.


The hereditary cerebellar ataxias are a clinically and genetically heterogeneous group of disorders that primarily affect the cerebellum; often there are additional features such as neuropathy, cognitive decline, or maculopathy that help define the clinical subtype of ataxia. They are commonly classified according to their mode of inheritance into autosomal dominant, autosomal recessive, X-linked, and mitochondrial forms. Great advances have been made in understanding the genetics of cerebellar ataxias in the last 15 years. At least 36 different forms of ADCA are known, 20 autosomal-recessive, two X-linked, and several forms of ataxia associated with mitochondrial defects are known to date. However, in about 40 % of suspected genetically determined ataxia cases, the underlying genetic defect remains undetermined. Although the majority of disease genes have been found in the last two decades, over the last 2 years the genetics has undergone a methodological revolution. New DNA sequencing technologies are enabling us to investigate the whole or large targeted proportions of the genome in a rapid, affordable, and comprehensive way. Exome and targeted sequencing has recently identified four new genes causing ataxia: TGM6, ANO10, SYT14, and rundataxin. This approach is likely to continue to discover new ataxia genes and make screening of existing genes more effective. Translating the genetic findings into isolated and overlapping disease pathways will help stratify patient groups and identify therapeutic targets for ataxia that have so far remained undiscovered.

Publication types

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

MeSH terms

  • Animals
  • Cerebellar Ataxia / classification
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / genetics*
  • Exome / genetics
  • Genetic Linkage
  • Genetics, Medical*
  • Humans
  • Mutation / genetics*
  • Translational Research, Biomedical / methods
  • Translational Research, Biomedical / trends