Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction

0524742 - FGÚ 2021 RIV CH eng J - Journal Article
Kubánek, M. - Schimerová, T. - Piherová, L. - Brodehl, A. - Krebsová, A. - Ratnavadivel, S. - Stanasiuk, C. - Hansíková, H. - Zeman, J. - Paleček, T. - Houštěk, Josef - Drahota, Zdeněk - Nůsková, Hana - Mikešová, Jana - Zámečník, J. - Macek Jr., M. - Ridzoň, P. - Malusková, J. - Stránecký, V. - Melenovský, V. - Milting, H. - Kmoch, S.
Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction.
Journal of Clinical Medicine. Roč. 9, č. 4 (2020), č. článku 937. E-ISSN 2077-0383
R&D Projects: GA MZd(CZ) NV17-28784A
Institutional support: RVO:67985823
Keywords : desmin * dilated cardiomyopathy * mitochondrial dysfunction * myopathy * non-ischemic cardiomyopathy * whole exome sequencing
OECD category: Cardiac and Cardiovascular systems
Impact factor: 4.242, year: 2020
Method of publishing: Open access
https://www.mdpi.com/2077-0383/9/4/937

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.
Permanent Link: http://hdl.handle.net/11104/0309045