title: DOK7 mutations presenting as a proximal myopathy in French Canadians.
abstract: DOK7 mutations cause a congenital myasthenic syndrome (OMIM 254300) characterized by a "limb-girdle" phenotype. We identified 7 French-Canadian patients with a previously undiagnosed proximal myopathy. A genome wide scan was performed. Homozygosity mapping identified a locus on chromosome 4p16.2 containing DOK7. Sequencing of DOK7 revealed homozygous 1124_1127dupTGCC mutations in all individuals. SNP genotyping of 42kb surrounding DOK7 in our cohort and in 9 patients of various European origins demonstrated a shared haplotype suggesting a common ancestral European mutation. In our cohort, fatigability was not prominent; rather patients reported prolonged periods of increased weakness. Abnormalities on repetitive nerve stimulation and single fiber EMG were not invariably present. There was considerable intra-familial phenotypic variability, and we report an asymptomatic individual. DOK7 mutations should be considered in patients with early-onset myopathy, even in the absence of symptoms suggesting a possible myasthenia.
authors.affiliation: Laboratoire de neurogénétique de la motricité, Centre de recherche du CHUM, Montréal, Université de Montréal, QC, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Srour
authors.forename: Véronique
authors.initials: V
authors.lastname: Bolduc
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Daniel
authors.initials: D
authors.lastname: Gendron
authors.forename: Michael I
authors.initials: MI
authors.lastname: Shevell
authors.forename: Chantal
authors.initials: C
authors.lastname: Poulin
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: D000293:Adolescent; D002170:Canada / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D002894:Chromosomes, Human, Pair 4; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage / Q000502:physiology; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics*; D044465:White People; D055815:Young Adult
chemical_list: C511692:DOK7 protein, human; D009124:Muscle Proteins