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 language | English (US) |
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Pages (from-to) | 1627-1631 |
Number of pages | 5 |
Journal | Journal of Clinical Neuroscience |
Volume | 21 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2014 |
Externally published | Yes |
Keywords
- AOA2
- Autosomal recessive cerebellar ataxia
- DNA repair
- Helicase
- Senataxin
ASJC Scopus subject areas
- Surgery
- Neurology
- Clinical Neurology
- Physiology (medical)