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

Schirmer I, Dieding M, Klauke B, Brodehl A, Gärtner-Rommel A, Walhorn V, Gummert J, Schulz U, Paluszkiewicz L, Anselmetti D, Milting H (2018)
Molecular Genetics & Genomic Medicine 6(2): 288-293.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Autor/in
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Abstract / Bemerkung
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.
Stichworte
cardiomyopathy; cardiovascular genetics; desmin; intermediate filament proteins; skeletal myopathy
Erscheinungsjahr
2018
Zeitschriftentitel
Molecular Genetics & Genomic Medicine
Band
6
Ausgabe
2
Seite(n)
288-293
ISSN
2324-9269
Page URI
https://pub.uni-bielefeld.de/record/2916928

Zitieren

Schirmer I, Dieding M, Klauke B, et al. A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine. 2018;6(2):288-293.
Schirmer, I., Dieding, M., Klauke, B., Brodehl, A., Gärtner-Rommel, A., Walhorn, V., Gummert, J., et al. (2018). A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine, 6(2), 288-293. doi:10.1002/mgg3.358
Schirmer, I., Dieding, M., Klauke, B., Brodehl, A., Gärtner-Rommel, A., Walhorn, V., Gummert, J., Schulz, U., Paluszkiewicz, L., Anselmetti, D., et al. (2018). A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine 6, 288-293.
Schirmer, I., et al., 2018. A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine, 6(2), p 288-293.
I. Schirmer, et al., “A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy”, Molecular Genetics & Genomic Medicine, vol. 6, 2018, pp. 288-293.
Schirmer, I., Dieding, M., Klauke, B., Brodehl, A., Gärtner-Rommel, A., Walhorn, V., Gummert, J., Schulz, U., Paluszkiewicz, L., Anselmetti, D., Milting, H.: A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy. Molecular Genetics & Genomic Medicine. 6, 288-293 (2018).
Schirmer, Ilona, Dieding, Mareike, Klauke, Bärbel, Brodehl, Andreas, Gärtner-Rommel, Anna, Walhorn, Volker, Gummert, Jan, Schulz, Uwe, Paluszkiewicz, Lech, Anselmetti, Dario, and Milting, Hendrik. “A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy”. Molecular Genetics & Genomic Medicine 6.2 (2018): 288-293.
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