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Mol Genet Genomic Med. 2018 Mar;6(2):288-293. doi: 10.1002/mgg3.358. Epub 2017 Dec 23.

A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy.

Author information

1
Erich and Hanna Klessmann Institute for Cardiovascular Research & Development (EHKI), Heart and Diabetes Centre NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany.
2
Faculty of Physics, Experimental Biophysics and Applied Nanoscience, Bielefeld Institute for Nanoscience (BINAS), Bielefeld University, Bielefeld, Germany.

Abstract

BACKGROUND:

DES mutations cause different cardiac and skeletal myopathies. Most of them are missense mutations.

METHODS:

Using a next-generation sequencing cardiac 174 gene panel, we identified a novel heterozygous in-frame indel mutation (DES-c.493_520del28insGCGT, p.Q165_A174delinsAS) in a Caucasian patient with cardiomyopathy in combination with atrioventricular block and skeletal myopathy. This indel mutation is located in the coding region of the first exon. Family anamnesis revealed a history of sudden cardiac death. We performed cell transfection experiments and in vitro assembly experiments to prove the pathogenicity of this novel DES indel mutation.

RESULTS:

These experiments revealed a severe filament formation defect of mutant desmin supporting the pathogenicity. In addition, we labeled a skeletal muscle biopsy from the mutation carrier revealing cytoplasmic desmin positive protein aggregates. In summary, we identified and functionally characterized a pathogenic DES indel mutation causing cardiac and skeletal myopathy.

CONCLUSION:

Our study has relevance for the clinical and genetic interpretation of further DES indel mutations causing cardiac or skeletal myopathies and might be helpful for risk stratification.

KEYWORDS:

cardiomyopathy; cardiovascular genetics; desmin; intermediate filament proteins; skeletal myopathy

PMID:
29274115
PMCID:
PMC5902401
DOI:
10.1002/mgg3.358
[Indexed for MEDLINE]
Free PMC Article

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