Abstract |
Senataxin recently was identified as the mutated gene in ataxia-oculomotor apraxia 2, which is characterized by ataxia, oculomotor apraxia, and increased alpha-fetoprotein levels. In this study, we evaluated 24 ataxic patients from 10 French-Canadian families. All cases have a homogeneous phenotype consisting of a progressive ataxia appearing between 2 and 20 (mean age, 14.8) years of age with associated dysarthria, saccadic ocular pursuit, distal amyotrophy, sensory and motor neuropathy, and increased alpha-fetoprotein levels but absence of oculomotor apraxia. Linkage disequilibrium was observed with markers in the ataxia-oculomotor apraxia 2 locus on chromosome 9q34. We have identified four mutations in senataxin in the French-Canadian population including two novel missense mutations: the 5927T-->G mutation changes the leucine encoded by codon 1976 to an arginine in the helicase domain (L1976R), and the 193G-->A mutation changes a glutamic acid encoded by codon 65 into a lysine in the N-terminal domain of the protein (E65K). The common L1976R mutation is shared by 17 of 20 (85%) carrier chromosomes. The study of this large French-Canadian cohort better defines the phenotype of this ataxia and presents two novel mutations in senataxin including the more common founder mutation in the French-Canadian population.
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Authors | Antoine Duquette, Katel Roddier, Julia McNabb-Baltar, Isabelle Gosselin, Anik St-Denis, Marie-Josée Dicaire, Lina Loisel, Damian Labuda, Luc Marchand, Jean Mathieu, Jean-Pierre Bouchard, Bernard Brais |
Journal | Annals of neurology
(Ann Neurol)
Vol. 57
Issue 3
Pg. 408-14
(Mar 2005)
ISSN: 0364-5134 [Print] United States |
PMID | 15732101
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Multifunctional Enzymes
- alpha-Fetoproteins
- Glutamic Acid
- Arginine
- SETX protein, human
- DNA Helicases
- RNA Helicases
- Leucine
- Lysine
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Topics |
- Adult
- Aged
- Apraxias
(complications, genetics)
- Arginine
(genetics)
- Ataxia
(complications, genetics)
- Chromosomes, Human, Pair 9
- Cluster Analysis
- DNA Helicases
- DNA Mutational Analysis
(methods)
- Family Health
- Female
- Glutamic Acid
(genetics)
- Humans
- Leucine
(genetics)
- Linkage Disequilibrium
- Lysine
(genetics)
- Male
- Middle Aged
- Multifunctional Enzymes
- Mutation
(genetics)
- Oculomotor Nerve Diseases
(complications, genetics)
- Quebec
- RNA Helicases
(genetics)
- alpha-Fetoproteins
(metabolism)
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