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

Autor: Kubánek M; Department of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic., Schimerová T; Department of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.; Institute of Physiology, First Faculty of Medicine, Charles University, 11636 Prague, Czech Republic., Piherová L; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, 11636 Prague, Czech Republic., Brodehl A; Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, Germany., Krebsová A; Department of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic., Ratnavadivel S; Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, Germany., Stanasiuk C; Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, Germany., Hansíková H; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech Republic., Zeman J; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech Republic., Paleček T; 2nd Department of Medicine-Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech Republic., Houštěk J; Institute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech Republic., Drahota Z; Institute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech Republic., Nůsková H; Institute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech Republic., Mikešová J; Institute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech Republic., Zámečník J; Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University, 11636 Prague, Czech Republic., Macek M Jr; Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University, 11636 Prague, Czech Republic., Ridzoň P; Department of Neurology, Thomayer's Hospital, 14059 Prague, Czech Republic., Malusková J; Department of Pathology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic; Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic., Stránecký V; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, 11636 Prague, Czech Republic., Melenovský V; Department of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic., Milting H; Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, Germany., Kmoch S; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, 11636 Prague, Czech Republic.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2020 Mar 29; Vol. 9 (4). Date of Electronic Publication: 2020 Mar 29.
DOI: 10.3390/jcm9040937
Abstrakt: 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.
Databáze: MEDLINE
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