Molecular pathogenesis of Friedreich ataxia

Arch Neurol. 1999 Oct;56(10):1201-8. doi: 10.1001/archneur.56.10.1201.

Abstract

Friedreich ataxia, the most common type of inherited ataxia, is itself caused in most cases by a large expansion of an intronic GAA repeat, resulting in decreased expression of the target frataxin gene. The autosomal recessive inheritance of the disease gives this triplet repeat mutation some unique features of natural history and evolution. Frataxin is a mitochondrial protein that has homologues in yeast and even in gram-negative bacteria. Yeast organisms deficient in the frataxin homologue accumulate iron in mitochondria and show increased sensitivity to oxidative stress. This suggests that Friedreich ataxia is caused by mitochondrial dysfunction and free radical toxicity.

Publication types

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

MeSH terms

  • Frataxin
  • Friedreich Ataxia / etiology*
  • Friedreich Ataxia / genetics*
  • Friedreich Ataxia / metabolism
  • Humans
  • Iron-Binding Proteins*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*

Substances

  • Iron-Binding Proteins
  • Phosphotransferases (Alcohol Group Acceptor)