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- Title
Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction.
- Authors
Kubánek, Miloš; Schimerová, Tereza; Piherová, Lenka; Brodehl, Andreas; Krebsová, Alice; Ratnavadivel, Sandra; Stanasiuk, Caroline; Hansíková, Hana; Zeman, Jiří; Paleček, Tomáš; Houštěk, Josef; Drahota, Zdeněk; Nůsková, Hana; Mikešová, Jana; Zámečník, Josef; Macek, Milan; Ridzoň, Petr; Malusková, Jana; Stránecký, Viktor; Melenovský, Vojtěch
- Abstract
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.
- Subjects
MATHEMATICAL complexes; SKELETAL muscle; DIAGNOSIS; PHENOTYPES; MITOCHONDRIAL pathology; CARDIOMYOPATHIES; SKELETAL muscle injuries
- Publication
Journal of Clinical Medicine, 2020, Vol 9, Issue 4, p937
- ISSN
2077-0383
- Publication type
Article
- DOI
10.3390/jcm9040937