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A novel mutation of aprataxin associated with ataxia ocular apraxia type 1: phenotypical and genotypical characterization
- Source :
- Journal of the neurological sciences. 260(1-2)
- Publication Year :
- 2007
-
Abstract
- Ataxia oculomotor apraxia type 1 (AOA1) is the most common form of autosomal recessive ataxia in Japan, and the second in Portugal after Friedreich ataxia. AOA1 is typically characterized by early-onset cerebellar ataxia, oculomotor apraxia, hypoalbuminemia, hypercholesterolemia and late axonal sensori-motor neuropathy. AOA1 is associated with the aprataxin gene (APTX) encoding a protein involved in DNA repair. We characterized a novel homozygous missense mutation of APTX in a 34 year-old female patient born from consanguineous parents. The mutation, a Val230Gly caused by a c.689 T>G substitution, involved the histidine-triad (HIT) domain of the protein, affected a phylogenetically conserved amino acid and was absent in the control population. We described the clinical and neurophysiological features, the findings at structural and functional brain imaging, and the pathological picture of the sural nerve biopsy. The report emphasized the genetical and phenotypical heterogeneity of AOA1 by demonstrating atypical features such as absence of oculomotor apraxia and signs of pyramidal involvement. Expression studies by Western blotting on fibroblasts demonstrated that the homozygous Val230Gly mutation was associated with decreased levels of APTX indicating a loss-of-function mechanism.
- Subjects :
- genetica molecolare
Adult
Pathology
medicine.medical_specialty
Ataxia
genetic structures
Cerebellar Ataxia
Genotype
Apraxias
apratassina
DNA Mutational Analysis
aptX
Mutation, Missense
Consanguinity
Biology
Apraxia
Alcoholic Neuropathy
atassia
Ocular Motility Disorders
Cerebellum
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Genetic Testing
Oculomotor apraxia
Genetics
Aprataxin
Cerebellar ataxia
Nuclear Proteins
Electroencephalography
medicine.disease
Magnetic Resonance Imaging
Pedigree
DNA-Binding Proteins
Phenotype
Neurology
Amino Acid Substitution
Positron-Emission Tomography
Mutation
Female
Neurology (clinical)
medicine.symptom
Atrophy
Subjects
Details
- ISSN :
- 0022510X
- Volume :
- 260
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Journal of the neurological sciences
- Accession number :
- edsair.doi.dedup.....ad283b02179acbbcdea59d449e4b6083