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

作者：Schirmer Ilona; Dieding Mareike; Klauke Baerbel; Brodehl Andreas; Gaertner-Rommel Anna; Walhorn Volker; Gummert Jan; Schulz Uwe; Paluszkiewicz Lech; Anselmetti Dario; Milting Hendrik^*

来源：Molecular Genetics & Genomic Medicine, 2018, 6(2): 288-293.

DOI：10.1002/mgg3.358

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

BackgroundDES mutations cause different cardiac and skeletal myopathies. Most of them are missense mutations.
MethodsUsing 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 invitro assembly experiments to prove the pathogenicity of this novel DES indel mutation.
ResultsThese 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.
ConclusionOur 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.

• 出版日期2018-3