Ataxia with oculomotor apraxia type 2 fibroblasts exhibit increased susceptibility to oxidative DNA damage.
J Clin Neurosci
; 21(9): 1627-31, 2014 Sep.
Article
en En
| MEDLINE
| ID: mdl-24814856
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Ataxia Cerebelosa
/
Estrés Oxidativo
/
Síndrome de Cogan
/
Fibroblastos
Límite:
Female
/
Humans
/
Middle aged
País/Región como asunto:
America do sul
/
Colombia
Idioma:
En
Revista:
J Clin Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2014
Tipo del documento:
Article