Aim. To study the diagnostic significance of genetic testing in patients with dilated cardiomyopathy (DCM), identify predictors of life-threatening ventricular tachyarrhythmias (VTAs) and assess adverse clinical outcomes in different genetic groups.Material and methods. The study included 126 unrelated patients with verified DCM as follows: 70 (55,6%) probands with criteria for familial DCM and 56 (44,4%) individuals with a probable hereditary component. All patients (age, 43,1±11,3 years; men, 92 (73%); left ventricular ejection fraction, 30,6±8,43%; left ventricular enddiastolic diameter, 68,3±8,36 mm; follow-up period — median, 49 months) receive a complex of diagnostic investigations, including genetic screening using nextgeneration sequencing, followed by verification of variants by the Sanger method.Results. Pathogenic and likely pathogenic genetic variants were found in 61 (48,4%) of 126 patients with DCM. The dominant mutations were titin-truncating variants (TTNtvs), identified in 16 individuals (12,7%), and variants of lamin A/C (LMNA), identified in 13 probands (10,3%). Mutations in the other 19 genes were found in 32 (25,4%) patients. The following primary endpoints were assessed: sudden cardiac death (SCD), episodes of VTA (sustained ventricular tachycardia/ventricular fibrillation) and appropriate shocks of implanted cardiac resynchronization therapy (CRT)/cardioverter defibrillators (CVD) devices. As a result of ROC analysis, the following independent risk factors for SCD were identified: mutations in the LMNA gene (AUC, 0,760; p=0,0001) and non-sustained ventricular tachycardia (cut-off heart rate ≥161 bpm: AUC, 0,788; p=0,0001). When comparing the phenotypes and genotypes of DCM, TTNtv genotype was associated with a lower prevalence of complete left bundle branch block (χ2=7,46; p=0,024), a lower need for CRT/CVD implantation (χ2=5,70; p=0,017) and more rare episodes of sustained ventricular tachycardia/ventricular fibrillation (χ2=30,1; p=0,0001) compared with LMNA carriers. Kaplan-Meier analysis showed the worst prognosis in carriers of LMNA mutations both in relation to life-threatening VTA (log rang χ2=88,5; p=0,0001) and in achieving all unfavorable outcomes (χ2=27,8; p=0,0001) compared with groups of genenegative individuals, carriers of TTNtv and other genotypes.Conclusion. The phenotypes of DCM with TTNtv did not significantly differ in the incidence of VTAs and adverse outcomes compared with the gene-negative group and other genotypes (with the exception of LMNA). The contribution of the associations of LMNA mutations with VTAs on prognosis was confirmed, which shows the important role of LMNA genotype diagnosis for SCD risk stratification in patients with DCM.

Dilated cardiomyopathy (DCM) is a complex, etiologically heterogeneous myocardial disease, which is one of the main causes of heart failure and heart transplantation. In 2016, experts from the European working group proposed a new definition of cardiomyopathy, which includes intermediate variants with a change in phenotype in carriers of mutations from subclinical form to the full manifestations of the disease. The classification of DCM was supplemented with intermediate phenotypes with the inclusion of a hypokinetic form with reduced contractile function without ventricular dilatation and variants with predominant dilation or arrhythmogenicity. Pathological architectonics of DCM consists of many genetic determinants that interact with numerous environmental factors. Clinical manifestations depend not only on the malignancy and penetrance of the gene mutation, but also on a number of other causes — epigenomic factors, age, toxic effects, environmental aggressiveness, pregnancy, and the effects of other acquired diseases. The article summarizes the current epidemiological data and ideas about specific molecular changes with an unfavorable prognosis. For clarity, we present clinical observations of familial DCM with mutations in the RBM20 and LMNA genes.

Non-compaction cardiomyopathy (NCM) is a rare heart disease characterized by a two-layered ventricular wall, comprising a thinner compact epicardial layer and an inner non-compacted layer. However, only structural and morphological data without a thorough clinical assessment does not determine the NCM (regardless of the diagnostic criterion used).Aim. To study the NCM-related genes, phenotypic and genetic correlations, predictors of life-threatening ventricular tachyarrhythmias (VTA) and adverse clinical outcomes.Material and methods. Of 93 individuals with identified morphological criteria of NCM (median follow-up, 5 years), the study included 60 unrelated patients (38,5±13,8 years of age; men, 33 (55%); left ventricular ejection fraction (LVEF), 42,1±12,9%) with clinical verification of NCM (>1 obligate phenotypic trait). Adverse cardiovascular events were taken as the composite end point: life-threatening VTA, death, heart transplantation.Results. Pathogenic (or probably pathogenic) mutations were detected in 33 (55%) patients with NCM. The most common variants (57,9%) were identified in the sarcomere protein genes (TTN, MYBPC3, MYH7); digenic mutations were found in 21,6% of patients. Digenic mutations were associated with low LVEF and the highest risk of systolic dysfunction (OR, 38; 95% CI, 4,74-305; p=0,0001). Multivariate regression provided a predictive model (R=0,90; R2=0,81; F (5,41) =34,8; p<0,0001) and independent predictors of adverse clinical outcomes of NCM (genetic cause of the disease (pathogenic mutation), LV systolic dysfunction, myocardial fibrosis in 2 or more ventricular segments, and QRS prolongation. Regression and ROC-analysis identified electrical predictors of life-threatening VTA (fragmented QRS, QT prolongation, spatial QRS-T angle increase) and morphofunctional markers (myocardial fibrosis, systolic dysfunction).Conclusion. The study revealed a significant clinical and genetic heterogeneity of NCM with predominant mutations in the sarcomeric protein genes and determined the criteria for identification and prognosis of NCM.

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сравнение полных последовательностей геномов хлоропластов и митохондрий диких (Hordeum vulgare subsp. spontaneum) и культурных (Hordeum vulgare subsp. vulgare) образцов ячменя с целью оценки их внутривидового разнообразия. Объектами исследования стали 17 образцов ячменя, для которых было проведено секвенирование нового поколения (next generation sequencing-NGS) хлоропластной и примеси митохондриальной ДНК, полученных из фракции хлоропластов, изолированной методом дифференциального центрифугирования. Изучено также 5 полных последовательностей хлоропластного и 2-митохондриального геномов ячменя, доступных в базе данных NCBI GenBank. При обработке полученных NGS-данных учитывали области гомологии внутри и между геномами. Сравнительный анализ 22 хлоропластных геномов ячменя (10 H. vulgare subsp. vulgare и 12 H. vulgare subsp. spontaneum) выявил 107 полиморфных локусов: 9 INDEL (insertion or deletion), 79 SNP (single nucleotide polymorphism) и 19 полиморфизмов SSR-областей (simple sequence repeats). Из найденных SNP хлоропластного генома 20 были локализованы в экзонах генов. Анализ 19 полных последовательностей митохондриальных геномов (8 H. vulgare subsp. vulgare и 11 H. vulgare subsp. spontaneum) показал более низкий уровень изменчивости данных органелл внутри вида: 1 INDEL и 22 SNP. Из 4 найденных в экзонах SNP 2 приходились на кодирующую область одного из генов малой субъединицы рибосом и 2 были расположены в экзоне псевдогена. В результате исследования обнаружена высокая вариабельность хлоропластных геномов Hordeum vulgare при относительно низкой изменчивости митохондриальных геномов внутри данного вида. Выявлен ряд полиморфных локусов хлоропластного и митохондриального геномов, которые могут быть использованы для внутривидовой идентификации и филогенетических исследований. Доказана эффективность метода NGS смесей хлоропластной и митохондриальной ДНК для получения полных последовательностей органельных геномов ячменя. Ключевые слова: ячмень, хлоропластный геном, митохондриальный геном, секвенирование нового поколения, внутривидовое разнообразие Для цитирования: Оценкa изменчивости хлоропластных и митохондриальных геномов ячменя методом NGS-анализа органельных смесей / А. Е. Ермакович [и др.] // Вес. Нац. aкад. навук Беларусі.