DOK7 mutations presenting as a proximal myopathy in French Canadians

作者：Srour Myriam; Bolduc Veronique; Guergueltcheva Velina; Lochmueller Hanns; Gendron Daniel; Shevell Michael I; Poulin Chantal; Mathieu Jean; Bouchard Jean Pierre; Brais Bernard^*

来源：Neuromuscular Disorders, 2010, 20(7): 453-457.

DOI：10.1016/j.nmd.2010.05.007

• Congenital myasthenic syndrome
• DOK7
• Myopathy
• Neuromuscular transmission

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 42 kb 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.

• 出版日期2010-7