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Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region assessed by whole-exome sequencing and its clinical correlates.

Authors
  • Chaloupka, Anna1
  • Piherova, Lenka2
  • Grochova, Ilga1
  • Binova, Jana3
  • Krejci, Jan1
  • Spinarova, Lenka1
  • Stranecky, Viktor2
  • Kmoch, Stanislav2
  • Kubanek, Milos3
  • 1 1 st Internal Clinic of Cardio-angiology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic. , (Czechia)
  • 2 Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, 1 st Faculty of Medicine, Charles University, Prague, Czech Republic. , (Czechia)
  • 3 Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. , (Czechia)
Type
Published Article
Journal
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
Publication Date
Dec 01, 2019
Volume
163
Issue
4
Pages
309–317
Identifiers
DOI: 10.5507/bp.2018.054
PMID: 30275597
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology and clinical outcome. In this pilot study, we aimed to assess its genetic architecture and correlate genotype with left ventricular reverse remodelling (LVRR). In this multi-centre prospective observational study, we enrolled 83 Moravian patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing (WES). All patients underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as an absolute increase in left ventricular ejection fraction > 10% accompanied by a relative decrease of left ventricular end-diastolic diameter > 10% at 12 months. WES identified at least one disease-related variant in 45 patients (54%). LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncated variants, followed by individuals with a negative, or inconclusive WES and carriers of other disease-related variants (56% vs. 42% vs. 19%, P=0.041). A substantial proportion of RODCM cases have a monogenic or oligogenic genetic background. Carriers of non-titin disease-related variants are less likely to reach LVRR at 12- months than other individuals. Genetic testing could contribute to better prognosis prediction and individualized treatment of RODCM.

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