Evaluating the prevalence of polyglutamine repeat expansions in amyotrophic lateral sclerosis

Neurology. 2011 Jun 14;76(24):2062-5. doi: 10.1212/WNL.0b013e31821f4447. Epub 2011 May 11.

Abstract

Objective: Given the recent finding of an association between intermediate-length polyglutamine (polyQ) expansions in ataxin 2 and amyotrophic lateral sclerosis (ALS), we sought to determine whether expansions in other polyQ disease genes were associated with ALS.

Methods: We assessed the polyQ lengths of ataxin 1, ataxin 3, ataxin 6, ataxin 7, TBP, atrophin 1, and huntingtin in several hundred patients with sporadic ALS and healthy controls.

Results: Other than ataxin 2, we did not identify a significant association with the other polyQ genes and ALS.

Conclusions: These data indicate that the effects of ataxin 2 polyQ expansions on ALS risk are likely to be rooted in the biology of ataxin 2 or ataxin 2-specific interactions, rather than the presence of an expanded polyQ repeat per se. These findings have important consequences for understanding the role of ataxin 2 in ALS pathogenesis and provide a framework for future mechanistic studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Ataxin-1
  • Ataxin-3
  • Ataxin-7
  • Ataxins
  • Calcium Channels / genetics
  • DNA Repeat Expansion / genetics*
  • Humans
  • Huntingtin Protein
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Peptides / genetics*
  • Repressor Proteins / genetics
  • TATA-Box Binding Protein / genetics

Substances

  • ATXN1 protein, human
  • ATXN7 protein, human
  • Ataxin-1
  • Ataxin-7
  • Ataxins
  • CACNA1A protein, human
  • Calcium Channels
  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Peptides
  • Repressor Proteins
  • TATA-Box Binding Protein
  • TBP protein, human
  • atrophin-1
  • polyglutamine
  • ATXN3 protein, human
  • Ataxin-3