Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66725610.31857/S0016675824060101BXPGKHГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleNovel Frameshift Variant of the MYBPC3 Gene Associated with Hypertrophic Cardiomyopathy Significantly Decreases the Level of This Gene’s Transcript in the MyocardiumАссоциированный с гипертрофической кардиомиопатией новый вариант со сдвигом рамки считывания в гене MYBPC3 определяет значительное снижение уровня транскрипта этого гена в миокардеKiselevI. S.КиселевИ. С.
Russian Federation
kozinmax1992@gmail.comKozinM. S.КозинМ. С.
Russian Federation
kozinmax1992@gmail.comBaulinaN. M.БаулинаН. М.
Russian Federation
kozinmax1992@gmail.comSharipovaM. B.ШариповаМ. Б.
Uzbekistan
kozinmax1992@gmail.comZotovA. S.ЗотовА. С.
Russian Federation
kozinmax1992@gmail.comStepanovaE. A.СтепановаЕ. А.
Russian Federation
kozinmax1992@gmail.comKurilinaE. V.КурилинаЭ. В.
Russian Federation
kozinmax1992@gmail.comAbdullaevaG. Zh.АбдуллаеваГ. Ж.
Uzbekistan
kozinmax1992@gmail.comZateyshchikovD. A.ЗатейщиковД. А.
Russian Federation
kozinmax1992@gmail.comFavorovaO. O.ФавороваО. О.
Russian Federation
kozinmax1992@gmail.comChumakovaO. S.ЧумаковаО. С.
Russian Federation
kozinmax1992@gmail.comChazov National Medical Research Centre of CardiologyНациональный медицинский исследовательский центр кардиологии им. академика Е.И. Чазова Министерства здравоохранения Российской ФедерацииRegional Multidisciplinary Medical СenterБухарский областной многопрофильный медицинский центрRussian Medical Academy of Continuous Professional EducationРоссийская медицинская академия непрерывного профессионального образованияRepublican Specialized Scientific and Practical Medical Center of CardiologyРеспубликанский специализированный научно-практический медицинский центр кардиологииCity Clinical Hospital #17Городская клиническая больница № 17 Департамента здравоохранения города Москвы1606202460610611626022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/667256

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease with a prevalence of 1 : 200–1 : 500 in the general population. The majority of HCM-linked pathogenic (or likely pathogenic) variants is located in eight genes encoding proteins of sarcomere, the main contractile unit of cardiomyocytes; one of these genes, MYBPC3, is the most commonly affected and usually associated with the more benign clinical course of the disease compared to other HCM-related genes. Here, we describe a novel frame shift variant NM_000256.3:c.2781_2782insCACA of the MYBPC3 gene that causes familial HCM in the heterozygous state. The proband had a progressive heart failure despite the surgical removal of left ventricular tract obstruction. Evaluation of levels of transcripts produced from the mutant allele and wild-type allele of the MYBPC3 gene in proband myocardial tissue and comparison of their total levels with ones in the control samples from patients without HCM showed a significant allele-specific reduction of mutant transcript levels. Our results expand the spectrum of known genetic variants with a proven role in the development of HCM.

Гипертрофическая кардиомиопатия (ГКМП) ‒ самое распространенное наследственное заболевание сердца с частотой встречаемости 1 : 200–1 : 500 в общей популяции. В основе развития ГКМП в большинстве случаев лежат патогенные (или вероятно патогенные) варианты в восьми генах, кодирующих белки саркомера ‒ основной сократительной единицы кардиомиоцитов, и в первую очередь ‒ в гене MYBPC3; при этом варианты гена MYBPC3 часто ассоциированы с относительно доброкачественным клиническим течением заболевания. Здесь мы описываем новый вариант гена MYBPC3, приводящий вследствие мутации со сдвигом рамки считывания NM_000256.3:c.2781_2782insCACA в гетерозиготном состоянии к семейной ГКМП. У пробанда, несмотря на оперативное вмешательство по устранению обструкции левого желудочка, сохранялась прогрессирующая сердечная недостаточность. Оценка уровней транскриптов мутантного аллеля и аллеля дикого типа гена MYBPC3 в ткани миокарда пробанда, а также сравнение суммарного уровня транскриптов с контрольными образцами от пациентов без ГКМП показали значительное аллель-специфическое снижение уровня мутантного транскрипта. Полученные нами результаты расширяют спектр известных генетических вариантов с доказанной ролью в развитии ГКМП.

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