cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2020.4.n728cardio-728Research ArticleКЛИНИЧЕСКИЙ СЛУЧАЙCLINICAL CASE REPORTСмешанный фенотип: некомпактный миокард левого желудочка и гипертрофическая кардиомиопатияOverlapping Phenotype: Left Ventricular non-Compaction and Hypertrophic Cardiomyopathyhttps://orcid.org/0000-0001-9917-5932КомиссароваС. М.KomissarovaS. M.

ведущий научный сотрудник лаборатории хронической сердечной недостаточности РНПЦ «Кардиология»

доктор мед. наук, доцент

chief researcher of the laboratory of chronic heart failure of RSPC “Cardiology”

doctor of medicine

docent

kom_svet@mail.ruhttps://orcid.org/0000-0002-1986-1367РинейскаяН. М.RineiskaN. M.

младший научный сотрудник лаборатории хронической сердечной недостаточности РНПЦ “Кардиология”

врач второй квалификационной категории

junior researcher of the laboratory of chronic heart failure of RSPC “Cardiology”

doctor of the second qualification category

nadya.rin@gmail.comhttps://orcid.org/0000-0003-4721-9109ЧаковаН. Н.ChakovaN. N.

ведущий научный сотрудник института генетики и цитологии НАН Беларуси

кандидат биологических наук

leading researcher of the Institute of Genetics and Cytology of Belarus National Academy of Sciences

candidate of biology

n.chakova@igc.byhttps://orcid.org/0000-0002-3566-7644НиязоваС. С.NiyazovaS. S.

младший научный сотрудник института генетики и цитологии НАН Беларуси

junior researcher of the Institute of Genetics and Cytology of Belarus National Academy of Sciences

kruglenko_sveta@tut.byРНПЦ "Кардиология"БеларусьState Institution Republican Scientific and Practical Centre «Cardiology»BelarusРНПЦ «Кардиология»БеларусьState Institution Republican Scientific and Practical Centre «Cardiology»BelarusИнститут генетики и цитологии НАН БеларусиБеларусьInstitute of Genetics and Cytology of Belarus National Academy of SciencesBelarus202018032020604137145Copyright © Kardiomag, 20202020KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/728

Цель Изучить особенности клинического течения смешанного фенотипа (гипертрофическая кардиомиопатия – ГКМП и некомпактный миокард левого желудочка – НКМЛЖ), определить генетические причины и оценить частоту развития сердечно-сосудистых осложнений (ССО) за период наблюдения.Материал и методы При скрининговом обследовании 286 пациентов с ГКМП у 8 (2,8 %; медиана возраста 41,5 года, 4 мужчины и 4 женщины) из неродственных семей выявлен смешанный фенотип (сочетание ГКМП и НКМЛЖ). У их 10 родственников I степени родства наиболее частым фенотипом был ГКМП без НКМЛЖ, однако также наблюдались и фенотип изолированного варианта НКМЛЖ, и смешанный фенотип. Критерии НКМЛЖ и ГКМП были подтверждены с помощью эхокардиографии и магнитно-резонансной томографии сердца. Генотипирование проводили методом высокопроизводительного секвенирования NGS с использованием набора TruSight Cardio Sequencing Panel.Результаты Пробанды с сочетанием ГКМП и НКМЛЖ в сравнении с родственниками I степени родства c изолированными ГКМП и НКМЛЖ характеризовались более выраженной дисфункцией левого желудочка (фракция выброса 43,57±7,6 и 53,64±6,51 % соответственно; p<0,001) и увеличенным риском развития ССО: большей частотой желудочковых тахиаритмий (7,9 и 2,2 % соответственно; p<0,01). При смешанном фенотипе выявлено 11 мутаций в 5 генах у 8 пациентов, при этом 72,7 % мутаций находились в генах MYH7 и MYBPC3, кодирующих тяжелую цепь β-миозина и миозинсвязывающий белок С соответственно, однако в некоторых случаях дополнительно обнаружены замены и в других генах (DTNA, TGFB2).Заключение Смешанный фенотип (ГКМП и НКМЛЖ) связан с более тяжелым клиническим течением заболевания и неблагоприятными ССО.

Aim To study the clinical course of the mixed phenotype (hypertrophic cardiomyopathy, HCMP, and left ventricular noncompaction, LVNC); to determine its genetic causes; and to evaluate incidence of cardiovascular complications (CVC) during the follow-up period.Material and methods In screening of 286 patients with HCMP, 8 of them (2.8 %; median age, 41.5 years; 4 men and 4 women) from unrelated families were found to have the mixed phenotype (combination of HCMP and LVNC). For their 10 first-degree relatives, the most frequent phenotype was HCMP without LVNC; however, both isolated LVNC and the mixed phenotype were also observed. Criteria for HCMP and LVNC were confirmed by echocardiography and cardiac magnetic resonance imaging Genotyping was performed by high-throughput sequencing NGT using the TruSight Cardio Sequencing Panel kit.Results Probands with the HCMP+LVNC combination compared to first-degree relatives with isolated HCMP and LVNC were characterized by more pronounced left ventricular dysfunction (ejection fraction, 43.57±7.6 and 53.64±6.51 %, respectively; p<0.001), a higher risk of CVC, and a higher incidence of ventricular tachyarrhythmias (7.9 and 2.2 %, respectively; p<0.01). 11 mutations in 5 genes were found in 8 patients with the mixed phenotype. 72.7 % of mutations were in the MYH7 and MYBPC3 genes that encode the heavy chain of β-myosin and myosin-binding protein C, respectively; however, in some cases, replacements in other genes (DTNA, TGFB2) were also found.Conclusion The mixed phenotype (HCMP and LVNC) is associated with more severe clinical course of the disease and unfavorable CVC.

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The authors declare that there are no conflicts of interest present.