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Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects

2015; BioMed Central; Volume: 15; Issue: 1 Linguagem: Inglês

10.1186/s12883-015-0449-3

1471-2377

Jens A. Petersen, Thierry Küntzer, Dirk Fischer, Maja von der Hagen, Angela Huebner, Veronika Kana, Johannes Alexander Lobrinus, Wolfram Kreß, Elisabeth J. Rushing, Michael Sinnreich, Hans H. Jung,

Genetic Neurodegenerative Diseases

Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. 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 + 2T>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.2869C>T (p.Gln957Stop), c.5928G>A (p.Trp1976Stop)). Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c. 3031 + 2T>C) suggested a possible founder effect.