DOK7 mutations presenting as a proximal myopathy in French Canadians.
Neuromuscul Disord
; 20(7): 453-7, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20610155
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndromes Miastênicas Congênitas
/
Proteínas Musculares
/
Mutação
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article