Ataxia with oculomotor apraxia type 2 fibroblasts exhibit increased susceptibility to oxidative DNA damage

Ricardo H. Roda, Carlo Rinaldi, Rajat Singh, Alice B. Schindler, Craig Blackstone

Research output: Contribution to journalArticlepeer-review

Abstract

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive cerebellar ataxia associated with mutations in SETX, which encodes the senataxin protein, a DNA/RNA helicase. We describe the clinical phenotype and molecular characterization of a Colombian AOA2 patient who is compound heterozygous for a c.994 C>T (p.R332W) missense mutation in exon 7 and a c.6848-6851delCAGA (p.T2283KfsX32) frameshift deletion in SETX exon 21. Immunocytochemistry of patient-derived fibroblasts revealed a normal cellular distribution of the senataxin protein, suggesting that these mutations do not lead to loss or mis-localization of the protein, but rather that aberrant function of senataxin underlies the disease pathogenesis. Furthermore, we used the alkaline comet assay to demonstrate that patient-derived fibroblast cells exhibit an increased susceptibility to oxidative DNA damage. This assay provides a novel and additional means to establish pathogenicity of SETX mutations.

Original languageEnglish (US)
Pages (from-to)1627-1631
Number of pages5
JournalJournal of Clinical Neuroscience
Volume21
Issue number9
DOIs
StatePublished - Sep 2014
Externally publishedYes

Keywords

  • AOA2
  • Autosomal recessive cerebellar ataxia
  • DNA repair
  • Helicase
  • Senataxin

ASJC Scopus subject areas

  • Surgery
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

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