Mutations in rare ataxia genes are uncommon causes of sporadic cerebellar ataxia

Mov Disord. 2012 Mar;27(3):442-6. doi: 10.1002/mds.24064. Epub 2012 Jan 27.

Abstract

Background: Sporadic-onset ataxia is common in a tertiary care setting but a significant percentage remains unidentified despite extensive evaluation. Rare genetic ataxias, reported only in specific populations or families, may contribute to a percentage of sporadic ataxia.

Methods: Patients with adult-onset sporadic ataxia, who tested negative for common genetic ataxias (SCA1, SCA2, SCA3, SCA6, SCA7, and/or Friedreich ataxia), were evaluated using a stratified screening approach for variants in 7 rare ataxia genes.

Results: We screened patients for published mutations in SYNE1 (n = 80) and TGM6 (n = 118), copy number variations in LMNB1 (n = 40) and SETX (n = 11), sequence variants in SACS (n = 39) and PDYN (n = 119), and the pentanucleotide insertion of spinocerebellar ataxia type 31 (n = 101). Overall, we identified 1 patient with a LMNB1 duplication, 1 patient with a PDYN variant, and 1 compound SACS heterozygote, including a novel variant.

Conclusions: The rare genetic ataxias examined here do not significantly contribute to sporadic cerebellar ataxia in our tertiary care population.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cerebellar Ataxia / genetics*
  • Cytoskeletal Proteins
  • DNA Helicases
  • Databases, Bibliographic / statistics & numerical data
  • Enkephalins / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Heat-Shock Proteins / genetics*
  • Humans
  • Lamin Type B / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multifunctional Enzymes
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Phenotype
  • Protein Precursors / genetics*
  • RNA Helicases / genetics
  • Transglutaminases / genetics

Substances

  • Cytoskeletal Proteins
  • Enkephalins
  • Heat-Shock Proteins
  • Lamin Type B
  • Multifunctional Enzymes
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Protein Precursors
  • SACS protein, human
  • SYNE1 protein, human
  • preproenkephalin
  • TGM6 protein, human
  • Transglutaminases
  • SETX protein, human
  • DNA Helicases
  • RNA Helicases