Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects.

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.

• 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
• Journal: BMC neurology (BMC Neurol) Vol. 15 Pg. 182 (Oct 06 2015) ISSN: 1471-2377 [Electronic] England
• PMID: 26444858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DYSF protein, human
• Dysferlin
• Membrane Proteins
• Muscle Proteins

Topics

• Adolescent
• Adult
• Dysferlin
• Female
• Founder Effect
• Heterozygote
• Homozygote
• Humans
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Muscle Proteins (genetics)
• Muscular Dystrophies, Limb-Girdle (genetics)
• Mutation
• Phenotype
• Switzerland
• Young Adult