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Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects


Petersen, Jens A; Kuntzer, Thierry; Fischer, Dirk; von der Hagen, Maja; Huebner, Angela; Kana, Veronika; Lobrinus, Johannes A; Kress, Wolfram; Rushing, Elisabeth J; Sinnreich, Michael; Jung, Hans H (2015). Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects. BMC Neurology, 15(182):online.

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 + 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)).
CONCLUSIONS: 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.

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 + 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)).
CONCLUSIONS: 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:01 Dec 2015 12:01
Last Modified:08 Dec 2017 15:21
Publisher:BioMed Central
ISSN:1471-2377
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s12883-015-0449-3
PubMed ID:26444858

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