Dysferlinopathy in Switzerland: Clinical Phenotypes and Potential Founder Effects

Overview

Journal BMC Neurol

Publisher Biomed Central

Specialty Neurology

Date 2015 Oct 8

PMID 26444858

Citations 6

Authors

Jens A Petersen

Thierry Kuntzer

Dirk Fischer

Maja von der Hagen

Angela Huebner

Veronika Kana

Johannes A Lobrinus

Wolfram Kress

Elisabeth J Rushing

Michael Sinnreich

Hans H Jung

Affiliations

Soon will be listed here.

Abstract

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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