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

Published on Mar 1, 2018in Molecular Genetics & Genomic Medicine
· DOI :10.1002/mgg3.358
Ilona Schirmer3
Estimated H-index: 3
(RUB: Ruhr University Bochum),
Mareike Dieding6
Estimated H-index: 6
(Bielefeld University)
+ 8 AuthorsHendrik Milting26
Estimated H-index: 26
(RUB: Ruhr University Bochum)
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.
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#1Andreas Brodehl (RUB: Ruhr University Bochum)H-Index: 8
#2Anna Gaertner-Rommel (RUB: Ruhr University Bochum)H-Index: 4
Last.Dario Anselmetti (Bielefeld University)H-Index: 36
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#1Valerio Azzimato (Karolinska University Hospital)H-Index: 5
#2Nina Gennebäck (Karolinska University Hospital)H-Index: 1
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#2R. Ferrier (AHS: Alberta Health Services)H-Index: 2
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#1Sarah Köster (GAU: University of Göttingen)H-Index: 23
#2David A. Weitz (Harvard University)H-Index: 127
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