Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction
<b>Background:</b> 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...
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MDPI AG
2020-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/4/937 |
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| author | Miloš Kubánek Tereza Schimerová Lenka Piherová Andreas Brodehl Alice Krebsová Sandra Ratnavadivel Caroline Stanasiuk Hana Hansíková Jiří Zeman Tomáš Paleček Josef Houštěk Zdeněk Drahota Hana Nůsková Jana Mikešová Josef Zámečník Milan Macek Petr Ridzoň Jana Malusková Viktor Stránecký Vojtěch Melenovský Hendrik Milting Stanislav Kmoch |
| author_facet | Miloš Kubánek Tereza Schimerová Lenka Piherová Andreas Brodehl Alice Krebsová Sandra Ratnavadivel Caroline Stanasiuk Hana Hansíková Jiří Zeman Tomáš Paleček Josef Houštěk Zdeněk Drahota Hana Nůsková Jana Mikešová Josef Zámečník Milan Macek Petr Ridzoň Jana Malusková Viktor Stránecký Vojtěch Melenovský Hendrik Milting Stanislav Kmoch |
| author_sort | Miloš Kubánek |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Methods:</b> A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. <b>Results:</b> 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. <b>Conclusions:</b> The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases. |
| first_indexed | 2024-03-11T10:10:01Z |
| format | Article |
| id | doaj.art-9479034fcbfb4a94bc758a6f44f4de68 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T10:10:01Z |
| publishDate | 2020-03-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-9479034fcbfb4a94bc758a6f44f4de682023-11-16T14:36:20ZengMDPI AGJournal of Clinical Medicine2077-03832020-03-019493710.3390/jcm9040937Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial DysfunctionMiloš Kubánek0Tereza Schimerová1Lenka Piherová2Andreas Brodehl3Alice Krebsová4Sandra Ratnavadivel5Caroline Stanasiuk6Hana Hansíková7Jiří Zeman8Tomáš Paleček9Josef Houštěk10Zdeněk Drahota11Hana Nůsková12Jana Mikešová13Josef Zámečník14Milan Macek15Petr Ridzoň16Jana Malusková17Viktor Stránecký18Vojtěch Melenovský19Hendrik Milting20Stanislav Kmoch21Department of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicDepartment of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, 11636 Prague, Czech RepublicErich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, GermanyDepartment of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicErich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, GermanyErich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, GermanyDepartment of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech RepublicDepartment of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech Republic2nd Department of Medicine–Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech RepublicInstitute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech RepublicInstitute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech RepublicInstitute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech RepublicInstitute of Physiology, Czech Academy of Sciences, 11720 Prague, Czech RepublicDepartment of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University, 11636 Prague, Czech RepublicDepartment of Biology and Medical Genetics, Second Faculty of Medicine, Charles University, 11636 Prague, Czech RepublicDepartment of Neurology, Thomayer’s Hospital, 14059 Prague, Czech RepublicDepartment of Pathology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic; Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, 11636 Prague, Czech RepublicDepartment of Cardiology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech RepublicErich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, GermanyResearch Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, 11636 Prague, Czech Republic<b>Background:</b> 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. <b>Methods:</b> A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. <b>Results:</b> 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. <b>Conclusions:</b> The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases.https://www.mdpi.com/2077-0383/9/4/937desmindilated cardiomyopathymitochondrial dysfunctionmyopathynon-ischemic cardiomyopathywhole exome sequencing |
| spellingShingle | Miloš Kubánek Tereza Schimerová Lenka Piherová Andreas Brodehl Alice Krebsová Sandra Ratnavadivel Caroline Stanasiuk Hana Hansíková Jiří Zeman Tomáš Paleček Josef Houštěk Zdeněk Drahota Hana Nůsková Jana Mikešová Josef Zámečník Milan Macek Petr Ridzoň Jana Malusková Viktor Stránecký Vojtěch Melenovský Hendrik Milting Stanislav Kmoch Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction Journal of Clinical Medicine desmin dilated cardiomyopathy mitochondrial dysfunction myopathy non-ischemic cardiomyopathy whole exome sequencing |
| title | Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction |
| title_full | Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction |
| title_fullStr | Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction |
| title_full_unstemmed | Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction |
| title_short | Desminopathy: Novel Desmin Variants, a New Cardiac Phenotype, and Further Evidence for Secondary Mitochondrial Dysfunction |
| title_sort | desminopathy novel desmin variants a new cardiac phenotype and further evidence for secondary mitochondrial dysfunction |
| topic | desmin dilated cardiomyopathy mitochondrial dysfunction myopathy non-ischemic cardiomyopathy whole exome sequencing |
| url | https://www.mdpi.com/2077-0383/9/4/937 |
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