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Published on: August 20, 2019
Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects
Jens A Petersen1, Thierry Kuntzer2, Dirk Fischer3
1Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091, Zürich, Switzerland. jens.petersen@usz.ch.
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.
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