title: Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy.
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.
authors.affiliation: Laboratoire de Neurogénétique, M4211-L3, Centre de Recherche du CHUM, 1560 Sherbrooke est, Montreal, Quebec, Canada H2L 4M1.
authors.forename: Antoine
authors.initials: A
authors.lastname: Duquette
authors.forename: Katel
authors.initials: K
authors.lastname: Roddier
authors.forename: Julia
authors.initials: J
authors.lastname: McNabb-Baltar
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gosselin
authors.forename: Anik
authors.initials: A
authors.lastname: St-Denis
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Dicaire
authors.forename: Lina
authors.initials: L
authors.lastname: Loisel
authors.forename: Damian
authors.initials: D
authors.lastname: Labuda
authors.forename: Luc
authors.initials: L
authors.lastname: Marchand
authors.forename: Jean
authors.initials: J
authors.lastname: Mathieu
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bouchard
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
mesh_terms: D000328:Adult; D000368:Aged; D001072:Apraxias / Q000150:complications / Q000235:genetics; D001120:Arginine / Q000235:genetics; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D016000:Cluster Analysis; D004265:DNA Helicases; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000235:genetics; D015810:Linkage Disequilibrium; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D064251:Multifunctional Enzymes; D009154:Mutation / Q000235:genetics*; D015840:Oculomotor Nerve Diseases / Q000150:complications / Q000235:genetics*; D011792:Quebec; D020365:RNA Helicases / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D064251:Multifunctional Enzymes; D000509:alpha-Fetoproteins; D018698:Glutamic Acid; D001120:Arginine; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases; D007930:Leucine; D008239:Lysine