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Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction
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SYSNO ASEP 0524742 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction Author(s) Kubánek, M. (CZ)
Schimerová, T. (CZ)
Piherová, L. (CZ)
Brodehl, A. (DE)
Krebsová, A. (CZ)
Ratnavadivel, S. (DE)
Stanasiuk, C. (DE)
Hansíková, H. (CZ)
Zeman, J. (CZ)
Paleček, T. (CZ)
Houštěk, Josef (FGU-C) RID, ORCID
Drahota, Zdeněk (FGU-C) RID, ORCID
Nůsková, Hana (FGU-C) RID, ORCID
Mikešová, Jana (FGU-C) RID, ORCID
Zámečník, J. (CZ)
Macek Jr., M. (CZ)
Ridzoň, P. (CZ)
Malusková, J. (CZ)
Stránecký, V. (CZ)
Melenovský, V. (CZ)
Milting, H. (DE)
Kmoch, S. (CZ)Article number 937 Source Title Journal of Clinical Medicine. - : MDPI
Roč. 9, č. 4 (2020)Number of pages 19 s. Language eng - English Country CH - Switzerland Keywords desmin ; dilated cardiomyopathy ; mitochondrial dysfunction ; myopathy ; non-ischemic cardiomyopathy ; whole exome sequencing Subject RIV FA - Cardiovascular Diseases incl. Cardiotharic Surgery OECD category Cardiac and Cardiovascular systems R&D Projects NV17-28784A GA MZd - Ministry of Health (MZ) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000531821000044 DOI 10.3390/jcm9040937 Annotation Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2021 Electronic address https://www.mdpi.com/2077-0383/9/4/937
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