Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects

BACKGROUND: Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. METHODS: We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. RESULTS: Thirteen patients from 6 non-related families were included. Age of onset was 18.8 +/- 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2 T<C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869 C<T (p.Gln957Stop), c.5928 G<A (p.Trp1976Stop)). CONCLUSIONS: Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2 T<C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c. 3031 + 2 T<C) suggested a possible founder effect.