PT  - JOURNAL ARTICLE
AU  - Chaloupka, Anna
AU  - Piherova, Lenka
AU  - Grochova, Ilga
AU  - Binova, Jana
AU  - Krejci, Jan
AU  - Spinarova, Lenka
AU  - Stranecky, Viktor
AU  - Kmoch, Stanislav
AU  - Kubanek, Milos
TI  - Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region assessed by whole-exome sequencing and its clinical correlates
DP  - 2019 Dec 11
TA  - Biomedical papers
PG  - 309--317
VI  - 163
IP  - 4
AID - 10.5507/bp.2018.054
IS  - 12138118
AB  - Aims: 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). Patients and Methods: 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. Results: 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). Conclusion: 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.