ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2022-3-205-216ssmu-4922Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESФенотипическая вариабельность гипертрофической кардиомиопатии у носителей патогенного варианта p.Arg870His гена MYH7Phenotype variation of hypertrophic cardiomyopathy in carriers of the p.Arg870His pathogenic variant in the MYH7 genehttps://orcid.org/0000-0003-3824-3641КучерА. Н.KucherA. N.

Кучер Аксана Николаевна – доктор биологических наук, ведущий научный сотрудник, лаборатория популяционной генетики, НИИ медицинской генетики, Томский НИМЦ.

634050, Томск, ул. Набережная реки Ушайки, 10

10, Ushaika Embankment Str., Tomsk, 634050

aksana-kucher@medgenetics.ruhttps://orcid.org/0000-0001-7969-7020ВалиахметовН. Р.ValiakhmetovN. R.

Валиахметов Наиль Раушанович – аспирант, НИИ медицинской генетики, Томский НИМЦ.

634050, Томск, ул. Набережная реки Ушайки, 10

10, Ushaika Embankment Str., Tomsk, 634050

valiakhmetov.nail@medgenetics.ruhttps://orcid.org/0000-0002-9789-9555СалаховР. Р.SalakhovR. R.

Салахов Рамиль Ринатович – кандидат медицинских наук, научный сотрудник, лаборатория популяционной генетики, НИИ медицинской генетики, Томский НИМЦ; доцент, кафедра биохимии и молекулярной биологии с курсом КЛД, СибГМУ.

634050, Томск, ул. Набережная реки Ушайки, 10; 634050, Томск, Московский тракт, 2

10, Ushaika Embankment Str., Tomsk, 634050; 2, Moscow Trakt, Tomsk, 634050

ramil.salakhov@medgenetics.ruhttps://orcid.org/0000-0002-7692-9954ГолубенкоМ. В.GolubenkoM. V.

Голубенко Мария Владимировна – кандидат биологических наук, ст. научный сотрудник, лаборатория популяционной генетики, НИИ медицинской генетики, Томский НИМЦ.

634050, Томск, ул. Набережная реки Ушайки, 10

10, Ushaika Embankment Str., Tomsk, 634050

maria-golubenko@medgenetics.ruhttps://orcid.org/0000-0002-3081-9477ПавлюковаЕ. Н.PavlyukovaE. N.

Павлюкова Елена Николаевна – доктор медицинских наук, профессор, зав. отделением атеросклероза и хронической ишемической болезни сердца, Томский НИМЦ.

634012, Томск, ул. Киевская, 111а

111a, Kievskaya Str., Tomsk, 634012

pavluk@cardio-tomsk.ruhttps://orcid.org/0000-0002-0673-4094НазаренкоМ. С.NazarenkoM. S.

Назаренко Мария Сергеевна – доктор медицинских наук, руководитель лаборатории популяционной генетики, НИИ медицинской генетики, Томский НИМЦ; профессор, кафедра медицинской генетики, СибГМУ.

634050, Томск, ул. Набережная реки Ушайки, 10; 634050, Томск, Московский тракт, 2

10, Ushaika Embankment Str., Tomsk, 634050; 2, Moscow Trakt, Tomsk, 634050

maria.nazarenko@medgenetics.ruНаучно-исследовательский институт (НИИ) медицинской генетики, Томский национальный исследовательский медицинский центр (НИМЦ), Российская академия наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesRussian FederationНаучно-исследовательский институт (НИИ) медицинской генетики, Томский национальный исследовательский медицинский центр (НИМЦ), Российская академия наук; Сибирский государственный медицинский университет (СибГМУ)РоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center (NRMC), Russian Academy of Sciences; Siberian State Medical UniversityRussian FederationНаучно-исследовательский институт (НИИ) кардиологии, Томский национальный исследовательский медицинский центр (НИМЦ), Российская академия наукРоссияCardiology Research Institute, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesRussian Federation202215102022213205216Copyright © Кучер А.Н., Валиахметов Н.Р., Салахов Р.Р., Голубенко М.В., Павлюкова Е.Н., Назаренко М.С., 20222022Кучер А.Н., Валиахметов Н.Р., Салахов Р.Р., Голубенко М.В., Павлюкова Е.Н., Назаренко М.С.Kucher A.N., Valiakhmetov N.R., Salakhov R.R., Golubenko M.V., Pavlyukova E.N., Nazarenko M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/4922

Обзор посвящен анализу вариабельности клинических проявлений неоднократно зарегистрированного у пациентов с гипертрофической кардиомиопатией (ГКМП) патогенного варианта p.Arg870His гена MYH7. К анализу привлечены данные научных публикаций, полученных в результате поиска в базах данных PubMed, СlinVar, eLibrary.ru, а также собственные результаты. Выявлен широкий спектр фенотипических проявлений у носителей патогенного варианта p.Arg870His: от бессимптомного носительства до тяжелого течения, быстрого прогрессирования и ранней смерти. Обсуждаются возможные факторы, модифицирующие эффект патогенного варианта (доза патогенного варианта, наличие других неблагоприятных генетических вариантов и др.). Подчеркивается важность накопления информации о клинических особенностях течения ГКМП у носителей конкретных вариантов генов с целью уточнения их патогенности, выявления модифицирующих клиническую картину факторов, что имеет значение для определения тактики ведения пациентов с ГКМП, уточнения прогноза, определения стратегии обследования членов их семей.

The review analyzes variability of clinical manifestations of p.Arg870His in the MYH7 gene, which is repeatedly registered in patients with hypertrophic cardiomyopathy (HCM). The analysis involves the data from scientific publications obtained as a search result in the PubMed, СlinVar, and eLibrary.ru databases, as well as authors’ own results. A wide range of phenotypic manifestations have been revealed in carriers of p.Arg870His, from the asymptomatic to severe course, rapid progression, and early death. The review considers possible factors that modify the effect of the pathogenic variant (i.e. dosage of the pathogenic variant, the presence of other unfavorable genetic variants, etc.). The importance of accumulating information on the clinical features of HCM in the carriers of specific gene variants is emphasized in order to clarify their pathogenicity and to identify factors modifying the clinical outcome, which is important for the choice of the treatment strategy for HCM.

гипертрофическая кардиомиопатия (ГКМП)ген тяжелой цепи миозина (MYH7)hypertrophic cardiomyopathy (HCM)myosin heavy chain 7 (MYH7) geneРабота выполнена при финансовой поддержке РФФИ в рамках научного проекта (№ 20-315-90059) и гранта Президента Российской Федерации (МК-1093.2020.7)The study was supported by the RFBR grant within the research project No. 20-315-90059 and the grant awarded by the President of the Russian Federation (MK-1093.2020.7)ReferencesГабрусенко С.А., Гудкова А.Я., Козиолова Н.А., Александрова С.А., Берсенева М.И., Гордеев М.Л. и др. Гипертрофическая кардиомиопатия. Клинические рекомендации 2020. Российский кардиологический журнал. 2021;26(5):4541. DOI: 10.15829/1560-4071-2021-4541.Габрусенко С.А., Гудкова А.Я., Козиолова Н.А., Александрова С.А., Берсенева М.И., Гордеев М.Л. и др. Гипертрофическая кардиомиопатия. Клинические рекомендации 2020. Российский кардиологический журнал. 2021;26(5):4541. DOI: 10.15829/1560-4071-2021-4541.McKenna W.J., Judge D.P. Epidemiology of the inherited cardiomyopathies. Nat. Rev. Cardiol. 2021;18(1):22–36. DOI: 10.1038/s41569-020-0428-2.McKenna W.J., Judge D.P. Epidemiology of the inherited cardiomyopathies. Nat. Rev. Cardiol. 2021;18(1):22–36. DOI: 10.1038/s41569-020-0428-2.Rodríguez-Capitán J., Fernández-Meseguer A., Márquez-Camas P., García-Pinilla J.M., Calvo-Bonacho E., García-Margallo T. et al. Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population. Rev. Clin. Esp. (Barc.). 2021;221(6):315–322. DOI: 10.1016/j.rceng.2020.01.008.Rodríguez-Capitán J., Fernández-Meseguer A., Márquez-Camas P., García-Pinilla J.M., Calvo-Bonacho E., García-Margallo T. et al. Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population. Rev. Clin. Esp. (Barc.). 2021;221(6):315–322. DOI: 10.1016/j.rceng.2020.01.008.Moon I., Lee S.Y., Kim H.K., Han K.D., Kwak S., Kim M. et al. Trends of the prevalence and incidence of hypertrophic cardiomyopathy in Korea: A nationwide population-based cohort study. PLoS One. 2020;15(1):e0227012. DOI: 10.1371/journal.pone.0227012.Moon I., Lee S.Y., Kim H.K., Han K.D., Kwak S., Kim M. et al. Trends of the prevalence and incidence of hypertrophic cardiomyopathy in Korea: A nationwide population-based cohort study. PLoS One. 2020;15(1):e0227012. DOI: 10.1371/journal.pone.0227012.Li L., Bainbridge M.N., Tan Y., Willerson J.T., Marian A.J. A Potential oligogenic etiology of hypertrophic cardiomyopathy: A classic single-gene disorder. Circ. Res. 2017;120(7):1084– 1090. DOI: 10.1161/CIRCRESAHA.116.310559.Li L., Bainbridge M.N., Tan Y., Willerson J.T., Marian A.J. A Potential oligogenic etiology of hypertrophic cardiomyopathy: A classic single-gene disorder. Circ. Res. 2017;120(7):1084– 1090. DOI: 10.1161/CIRCRESAHA.116.310559.Cerrone M., Remme C.A., Tadros R., Bezzina C.R., Delmar M. Beyond the one gene-one disease paradigm: Complex genetics and pleiotropy in inheritable cardiac disorders. Circulation. 2019;140(7):595–610. DOI: 10.1161/CIRCULATIONAHA.118.035954.Cerrone M., Remme C.A., Tadros R., Bezzina C.R., Delmar M. Beyond the one gene-one disease paradigm: Complex genetics and pleiotropy in inheritable cardiac disorders. Circulation. 2019;140(7):595–610. DOI: 10.1161/CIRCULATIONAHA.118.035954.Баулина Н.М., Киселёв И.С., Чумакова О.С., Фаворова О.О. Гипертрофическая кардиомиопатия как олигогенное заболевание: аргументы транскриптомики. Молекулярная биология. 2020;54(6):955–967. DOI: 10.31857/S0026898420060026.Баулина Н.М., Киселёв И.С., Чумакова О.С., Фаворова О.О. Гипертрофическая кардиомиопатия как олигогенное заболевание: аргументы транскриптомики. Молекулярная биология. 2020;54(6):955–967. DOI: 10.31857/S0026898420060026.Clinical Genome Resource. URL: https://clinicalgenome.org/Clinical Genome Resource. URL: https://clinicalgenome.org/Ingles J., Goldstein J., Thaxton C., Caleshu C., Corty E.W., Crowley S.B. et alEvaluating the clinical validity of hypertrophic cardiomyopathy genes. Circ. Genom. Precis Med. 2019;12(2):e002460. DOI: 10.1161/CIRCGEN.119.002460.Ingles J., Goldstein J., Thaxton C., Caleshu C., Corty E.W., Crowley S.B. et alEvaluating the clinical validity of hypertrophic cardiomyopathy genes. Circ. Genom. Precis Med. 2019;12(2):e002460. DOI: 10.1161/CIRCGEN.119.002460.ClinVar. URL: http://www.ncbi.nlm.nih.gov/clinvar/ClinVar. URL: http://www.ncbi.nlm.nih.gov/clinvar/Ниязова С.С., Чакова Н.Н., Комиссарова С.М., Сасинович М.А. Cпектр мутаций в генах саркомерных белков и их фенотипическое проявление у белорусских пациентов с гипертрофической кардиомиопатией. Медицинская генетика. 2019;18(6):21–33. DOI: 10.25557/2073-7998.2019.06.21-33.Ниязова С.С., Чакова Н.Н., Комиссарова С.М., Сасинович М.А. Cпектр мутаций в генах саркомерных белков и их фенотипическое проявление у белорусских пациентов с гипертрофической кардиомиопатией. Медицинская генетика. 2019;18(6):21–33. DOI: 10.25557/2073-7998.2019.06.21-33.Zou Y., Wang J., Liu X., Wang Y., Chen Y., Sun K. et al. Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. Mol. Biol. Rep. 2013;40(6):3969–3976. DOI: 10.1007/s11033-012-2474-2.Zou Y., Wang J., Liu X., Wang Y., Chen Y., Sun K. et al. Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. Mol. Biol. Rep. 2013;40(6):3969–3976. DOI: 10.1007/s11033-012-2474-2.Sedaghat-Hamedani F., Kayvanpour E., Tugrul O.F., Lai A., Amr A., Haas J. et al. Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals. Clin. Res. Cardiol. 2018;107(1):30– 41. DOI: 10.1007/s00392-017-1155-5.Sedaghat-Hamedani F., Kayvanpour E., Tugrul O.F., Lai A., Amr A., Haas J. et al. Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals. Clin. Res. Cardiol. 2018;107(1):30– 41. DOI: 10.1007/s00392-017-1155-5.Curila K., Benesova L., Penicka M., Minarik M., Zemanek D., Veselka J. et al. Spectrum and clinical manifestations of mutations in genes responsible for hypertrophic cardiomyopathy. Acta Cardiol. 2012;67(1):23–29. DOI: 10.1080/ac.67.1.2146562.Curila K., Benesova L., Penicka M., Minarik M., Zemanek D., Veselka J. et al. Spectrum and clinical manifestations of mutations in genes responsible for hypertrophic cardiomyopathy. Acta Cardiol. 2012;67(1):23–29. DOI: 10.1080/ac.67.1.2146562.Richmond C.M., James P.A., Pantaleo S.J., Chong B., Lunke S., Tan T.Y. et al. Clinical and laboratory reporting impact of ACMG-AMP and modified ClinGen variant classification frameworks in MYH7-related cardiomyopathy. Genet. Med. 2021;23(6):1108–1115. DOI: 10.1038/s41436-021-01107-y.Richmond C.M., James P.A., Pantaleo S.J., Chong B., Lunke S., Tan T.Y. et al. Clinical and laboratory reporting impact of ACMG-AMP and modified ClinGen variant classification frameworks in MYH7-related cardiomyopathy. Genet. Med. 2021;23(6):1108–1115. DOI: 10.1038/s41436-021-01107-y.Van Driest S.L., Ackerman M.J., Ommen S.R., Shakur R., Will M.L., Nishimura R.A. et al. Prevalence and severity of “benign” mutations in the beta-myosin heavy chain, cardiac troponin T, and alpha-tropomyosin genes in hypertrophic cardiomyopathy. Circulation. 2002;106(24):3085–3090. DOI: 10.1161/01.cir.0000042675.59901.14.Van Driest S.L., Ackerman M.J., Ommen S.R., Shakur R., Will M.L., Nishimura R.A. et al. Prevalence and severity of “benign” mutations in the beta-myosin heavy chain, cardiac troponin T, and alpha-tropomyosin genes in hypertrophic cardiomyopathy. Circulation. 2002;106(24):3085–3090. DOI: 10.1161/01.cir.0000042675.59901.14.Mori A.A., Castro L.R., Bortolin R.H., Bastos G.M., Oliveira V.F., Ferreira G.M. et al. Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy. Forensic. Sci. Int. Genet. 2021;52:102478. DOI: 10.1016/j.fsigen.2021.102478.Mori A.A., Castro L.R., Bortolin R.H., Bastos G.M., Oliveira V.F., Ferreira G.M. et al. Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy. Forensic. Sci. Int. Genet. 2021;52:102478. DOI: 10.1016/j.fsigen.2021.102478.Bashyam M.D., Savithri G.R., Gopikrishna M., Narasimhan C. A p.R870H mutation in the beta-cardiac myosin heavy chain 7 gene causes familial hypertrophic cardiomyopathy in several members of an Indian family. Can. J. Cardiol. 2007;23(10):788–790. DOI: 10.1016/s0828-282x(07)70828-0.Bashyam M.D., Savithri G.R., Gopikrishna M., Narasimhan C. A p.R870H mutation in the beta-cardiac myosin heavy chain 7 gene causes familial hypertrophic cardiomyopathy in several members of an Indian family. Can. J. Cardiol. 2007;23(10):788–790. DOI: 10.1016/s0828-282x(07)70828-0.Laredo R., Monserrat L., Hermida-Prieto M., Fernández X., Rodríguez I., Cazón L. et al. Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy. Rev. Esp. Cardiol. 2006;59(10):1008–1018. DOI: 10.1157/13093977.Laredo R., Monserrat L., Hermida-Prieto M., Fernández X., Rodríguez I., Cazón L. et al. Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy. Rev. Esp. Cardiol. 2006;59(10):1008–1018. DOI: 10.1157/13093977.Nishi H., Kimura A., Harada H., Koga Y., Adachi K., Matsuyama K. et al. A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy. Circulation. 1995;91(12):2911–2915. DOI: 10.1161/01.cir.91.12.2911.Nishi H., Kimura A., Harada H., Koga Y., Adachi K., Matsuyama K. et al. A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy. Circulation. 1995;91(12):2911–2915. DOI: 10.1161/01.cir.91.12.2911.Hershkovitz T., Kurolap A., Ruhrman-Shahar N., Monakier D., DeChene E.T., Peretz-Amit G. et al. Clinical diversity of MYH7-related cardiomyopathies: Insights into genotype-phenotype correlations. Am. J. Med. Genet A. 2019;179(3):365– 372. DOI: 10.1002/ajmg.a.61017.Hershkovitz T., Kurolap A., Ruhrman-Shahar N., Monakier D., DeChene E.T., Peretz-Amit G. et al. Clinical diversity of MYH7-related cardiomyopathies: Insights into genotype-phenotype correlations. Am. J. Med. Genet A. 2019;179(3):365– 372. DOI: 10.1002/ajmg.a.61017.Chung H., Kim Y., Cho S.M., Lee H.J., Park C.H., Kim J.Y. et al. Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathy. Mitochondrion. 2020;53:48–56. DOI: 10.1016/j.mito.2020.04.010.Chung H., Kim Y., Cho S.M., Lee H.J., Park C.H., Kim J.Y. et al. Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathy. Mitochondrion. 2020;53:48–56. DOI: 10.1016/j.mito.2020.04.010.Waldmüller S., Erdmann J., Binner P., Gelbrich G., Pankuweit S., Geier C. et al. Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure. Eur. J. Heart Fail. 2011;13(11):1185–1192. DOI: 10.1093/eurjhf/hfr074.Waldmüller S., Erdmann J., Binner P., Gelbrich G., Pankuweit S., Geier C. et al. Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure. Eur. J. Heart Fail. 2011;13(11):1185–1192. DOI: 10.1093/eurjhf/hfr074.Marsiglia J.D., Credidio F.L., de Oliveira T.G., Reis R.F., Antunes Mde O., de Araujo A.Q. et al. Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. Am. Heart J. 2013;166(4):775–782. DOI: 10.1016/j.ahj.2013.07.029.Marsiglia J.D., Credidio F.L., de Oliveira T.G., Reis R.F., Antunes Mde O., de Araujo A.Q. et al. Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. Am. Heart J. 2013;166(4):775–782. DOI: 10.1016/j.ahj.2013.07.029.Rai T.S., Ahmad S., Bahl A., Ahuja M., Ahluwalia T.S., Singh B. et al. Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy. Mol. Cell Biochem. 2009;321(1–2):189–196. DOI: 10.1007/s11010-008-9932-0.Rai T.S., Ahmad S., Bahl A., Ahuja M., Ahluwalia T.S., Singh B. et al. Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy. Mol. Cell Biochem. 2009;321(1–2):189–196. DOI: 10.1007/s11010-008-9932-0.De Feria A.E., Kott A.E., Becker J.R. Sarcomere mutation negative hypertrophic cardiomyopathy is associated with ageing and obesity. Open Heart. 2021;8(1):e001560. DOI: 10.1136/openhrt-2020-001560.De Feria A.E., Kott A.E., Becker J.R. Sarcomere mutation negative hypertrophic cardiomyopathy is associated with ageing and obesity. Open Heart. 2021;8(1):e001560. DOI: 10.1136/openhrt-2020-001560.Ниязова С.С., Чакова Н.Н., Михаленко Е.П., Чеботаре ва Н.В., Комиссарова С.М., Крупнова Э.В. Мутации в генах MYH7, MYBPC у пациентов с гипертрофической кардиомиопатией в Республике Беларусь. Молекулярная медицина. 2014;3:45–50.Ниязова С.С., Чакова Н.Н., Михаленко Е.П., Чеботаре ва Н.В., Комиссарова С.М., Крупнова Э.В. Мутации в генах MYH7, MYBPC у пациентов с гипертрофической кардиомиопатией в Республике Беларусь. Молекулярная медицина. 2014;3:45–50.Wang S., Zou Y., Fu C., Xu X., Wang J., Song L. et al. Worse prognosis with gene mutations of beta-myosin heavy chain than myosin-binding protein C in Chinese patients with hypertrophic cardiomyopathy. Clin. Cardiol. 2008;31(3):114–118. DOI: 10.1002/clc.20151.Wang S., Zou Y., Fu C., Xu X., Wang J., Song L. et al. Worse prognosis with gene mutations of beta-myosin heavy chain than myosin-binding protein C in Chinese patients with hypertrophic cardiomyopathy. Clin. Cardiol. 2008;31(3):114–118. DOI: 10.1002/clc.20151.Havndrup O., Bundgaard H., Andersen P.S., Allan Larsen L., Vuust J., Kjeldsen K. et al. Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations. Cardiovasc. Res. 2003;57(2):347–357. DOI: 10.1016/s0008-6363(02)00711-3.Havndrup O., Bundgaard H., Andersen P.S., Allan Larsen L., Vuust J., Kjeldsen K. et al. Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations. Cardiovasc. Res. 2003;57(2):347–357. DOI: 10.1016/s0008-6363(02)00711-3.Morales A., Ing A., Antolik C., Austin-Tse C., Baudhuin L.M., Bronicki L. et al. Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel. J. Mol. Diagn. 2021;23(5):589–598. DOI: 10.1016/j.jmoldx.2021.01.014.Morales A., Ing A., Antolik C., Austin-Tse C., Baudhuin L.M., Bronicki L. et al. Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel. J. Mol. Diagn. 2021;23(5):589–598. DOI: 10.1016/j.jmoldx.2021.01.014.Салахов Р.Р., Голубенко М.В., Павлюкова Е.Н., Кучер А.Н., Валиахметов Н.Р., Марков А.В. и др. Опыт молекулярно-генетической диагностики гипертрофической кардиомиопатии с использованием нанопорового секвенирования ДНК. Российский кардиологический журнал. 2021;26(10):4673. DOI: 10.15829/1560-4071-2021-4673.Салахов Р.Р., Голубенко М.В., Павлюкова Е.Н., Кучер А.Н., Валиахметов Н.Р., Марков А.В. и др. Опыт молекулярно-генетической диагностики гипертрофической кардиомиопатии с использованием нанопорового секвенирования ДНК. Российский кардиологический журнал. 2021;26(10):4673. DOI: 10.15829/1560-4071-2021-4673.Tanjore R.R., Sikindlapuram A.D., Calambur N., Thakkar B., Kerkar P.G., Nallari P. Genotype-phenotype correlation of R870H mutation in hypertrophic cardiomyopathy. Clin. Genet. 2006;69(5):434–436. DOI: 10.1111/j.1399-0004.2006.00599.x.Tanjore R.R., Sikindlapuram A.D., Calambur N., Thakkar B., Kerkar P.G., Nallari P. Genotype-phenotype correlation of R870H mutation in hypertrophic cardiomyopathy. Clin. Genet. 2006;69(5):434–436. DOI: 10.1111/j.1399-0004.2006.00599.x.Capek P., Vondrasek J., Skvor J., Brdicka R. Hypertrophic cardiomyopathy: from mutation to functional analysis of defective protein. Croat. Med. J. 2011;52(3):384–391. DOI: 10.3325/cmj.2011.52.384.Capek P., Vondrasek J., Skvor J., Brdicka R. Hypertrophic cardiomyopathy: from mutation to functional analysis of defective protein. Croat. Med. J. 2011;52(3):384–391. DOI: 10.3325/cmj.2011.52.384.Ferradini V., Parca L., Martino A., Lanzillo C., Silvetti E., Calò L. et al. Variants in MHY7 gene cause arrhythmogen ic cardiomyopathy. Genes. (Basel). 2021;12(6):793. DOI: 10.3390/genes12060793.Ferradini V., Parca L., Martino A., Lanzillo C., Silvetti E., Calò L. et al. Variants in MHY7 gene cause arrhythmogen ic cardiomyopathy. Genes. (Basel). 2021;12(6):793. DOI: 10.3390/genes12060793.Pommié C., Levadoux S., Sabatier R., Lefranc G., Lefranc M.P. IMGT standardized criteria for statistical analysis of immunoglobulin V-REGION amino acid properties. J. Mol. Recognit. 2004;17(1):17–32. DOI: 10.1002/jmr.647.Pommié C., Levadoux S., Sabatier R., Lefranc G., Lefranc M.P. IMGT standardized criteria for statistical analysis of immunoglobulin V-REGION amino acid properties. J. Mol. Recognit. 2004;17(1):17–32. DOI: 10.1002/jmr.647.Rayment I., Holden H.M., Sellers J.R., Fananapazir L., Epstein N.D. Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc. Natl. Acad. Sci. U S A. 1995;92(9):3864–3868. DOI: 10.1073/pnas.92.9.3864.Rayment I., Holden H.M., Sellers J.R., Fananapazir L., Epstein N.D. Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc. Natl. Acad. Sci. U S A. 1995;92(9):3864–3868. DOI: 10.1073/pnas.92.9.3864.Gruen M., Gautel M. Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C. J. Mol. Biol. 1999;286(3):933–949. DOI: 10.1006/jmbi.1998.2522.Gruen M., Gautel M. Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C. J. Mol. Biol. 1999;286(3):933–949. DOI: 10.1006/jmbi.1998.2522.Cuda G., Fananapazir L., Epstein N.D., Sellers J.R. The in vitro motility activity of beta-cardiac myosin depends on the nature of the beta-myosin heavy chain gene mutation in hypertrophic cardiomyopathy. J. Muscl. Res. Cell Motil. 1997;18(3):275–283. DOI: 10.1023/a:1018613907574.Cuda G., Fananapazir L., Epstein N.D., Sellers J.R. The in vitro motility activity of beta-cardiac myosin depends on the nature of the beta-myosin heavy chain gene mutation in hypertrophic cardiomyopathy. J. Muscl. Res. Cell Motil. 1997;18(3):275–283. DOI: 10.1023/a:1018613907574.GnomAD. URL: https://gnomad.broadinstitute.org/GnomAD. URL: https://gnomad.broadinstitute.org/AnanR.,ShonoH.,TeiC.Novelcardiacbeta-myosinheavychain gene missense mutations (R869C and R870C) that cause familial hypertrophic cardiomyopathy. Hum. Mutat. 2000;15(6):584. DOI: 10.1002/1098-1004(200006)15:6<584::AID-HUMU25>3.0.CO;2-R.AnanR.,ShonoH.,TeiC.Novelcardiacbeta-myosinheavychain gene missense mutations (R869C and R870C) that cause familial hypertrophic cardiomyopathy. Hum. Mutat. 2000;15(6):584. DOI: 10.1002/1098-1004(200006)15:6<584::AID-HUMU25>3.0.CO;2-R.Otsuka H., Arimura T., Abe T., Kawai H., Aizawa Y., Kubo T. et al. Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy. Circ. J. 2012;76(2):453–461. DOI: 10.1253/circj.cj-11-0876.Otsuka H., Arimura T., Abe T., Kawai H., Aizawa Y., Kubo T. et al. Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy. Circ. J. 2012;76(2):453–461. DOI: 10.1253/circj.cj-11-0876.Kaski J.P., Syrris P., Esteban M.T., Jenkins S., Pantazis A., Deanfield J.E. et al. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ. Cardiovasc. Genet. 2009;2(5):436–441. DOI: 10.1161/CIRCGENETICS.108.821314.Kaski J.P., Syrris P., Esteban M.T., Jenkins S., Pantazis A., Deanfield J.E. et al. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ. Cardiovasc. Genet. 2009;2(5):436–441. DOI: 10.1161/CIRCGENETICS.108.821314.Santos S., Marques V., Pires M., Silveira L., Oliveira H., Lança V. et al. High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort. BMC Med. Genet. 2012;13:17. DOI: 10.1186/1471-2350-13-17.Santos S., Marques V., Pires M., Silveira L., Oliveira H., Lança V. et al. High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort. BMC Med. Genet. 2012;13:17. DOI: 10.1186/1471-2350-13-17.Woo A., Rakowski H., Liew J.C., Zhao M.S., Liew C.C., Parker T.G. et al. Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart. 2003;89(10):1179–1185. DOI: 10.1136/heart.89.10.1179.Woo A., Rakowski H., Liew J.C., Zhao M.S., Liew C.C., Parker T.G. et al. Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart. 2003;89(10):1179–1185. DOI: 10.1136/heart.89.10.1179.McLeod C.J., Ackerman M.J., Nishimura R.A., Tajik A.J., Gersh B.J., Ommen S.R. Outcome of patients with hypertrophic cardiomyopathy and a normal electrocardiogram. J. Am. Coll. Cardiol. 2009;54(3):229–233. DOI: 10.1016/j.jacc.2009.02.071.McLeod C.J., Ackerman M.J., Nishimura R.A., Tajik A.J., Gersh B.J., Ommen S.R. Outcome of patients with hypertrophic cardiomyopathy and a normal electrocardiogram. J. Am. Coll. Cardiol. 2009;54(3):229–233. DOI: 10.1016/j.jacc.2009.02.071.Uchiyama K., Hayashi K., Fujino N., Konno T., Sakamoto Y., Sakata K. et al.. Impact of QT variables on clinical outcome of genotyped hypertrophic cardiomyopathy. Ann. Noninvasive Electrocardiol. 2009;14(1):65–71. DOI: 10.1111/j.1542474X.2008.00275.x.Uchiyama K., Hayashi K., Fujino N., Konno T., Sakamoto Y., Sakata K. et al.. Impact of QT variables on clinical outcome of genotyped hypertrophic cardiomyopathy. Ann. Noninvasive Electrocardiol. 2009;14(1):65–71. DOI: 10.1111/j.1542474X.2008.00275.x.Österberg A.W., Östman-Smith I., Jablonowski R., Carlsson M., Green H., Gunnarsson C. et al. High ECG riskscores predict late gadolinium enhancement on magnetic resonance imaging in HCM in the young. Pediatr. Cardiol. 2021;42(3):492–500. DOI: 10.1007/s00246-020-02506-9.Österberg A.W., Östman-Smith I., Jablonowski R., Carlsson M., Green H., Gunnarsson C. et al. High ECG riskscores predict late gadolinium enhancement on magnetic resonance imaging in HCM in the young. Pediatr. Cardiol. 2021;42(3):492–500. DOI: 10.1007/s00246-020-02506-9.Shimizu M., Ino H., Yamaguchi M., Terai H., Hayashi K., Kiyama M. et al. Chronologic electrocardiographic changes in patients with hypertrophic cardiomyopathy associated with cardiac troponin 1 mutation. Am. Heart J. 2002;143(2):289– 293. DOI: 10.1067/mhj.2002.119760.Shimizu M., Ino H., Yamaguchi M., Terai H., Hayashi K., Kiyama M. et al. Chronologic electrocardiographic changes in patients with hypertrophic cardiomyopathy associated with cardiac troponin 1 mutation. Am. Heart J. 2002;143(2):289– 293. DOI: 10.1067/mhj.2002.119760.Buja G., Miorelli M., Turrini P., Melacini P., Nava A. Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am. J. Cardiol. 1993;72(12):973–976. DOI: 10.1016/0002-9149(93)91118-2.Buja G., Miorelli M., Turrini P., Melacini P., Nava A. Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death. Am. J. Cardiol. 1993;72(12):973–976. DOI: 10.1016/0002-9149(93)91118-2.Enjuto M., Francino A., Navarro-López F., Viles D., Paré J.C., Ballesta A.M. Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene. J. Mol. Cell Cardiol. 2000;32(12):2307–2313. DOI: 10.1006/jmcc.2000.1260.Enjuto M., Francino A., Navarro-López F., Viles D., Paré J.C., Ballesta A.M. Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene. J. Mol. Cell Cardiol. 2000;32(12):2307–2313. DOI: 10.1006/jmcc.2000.1260.Erdmann J., Daehmlow S., Wischke S., Senyuva M., Werner U., Raible J. et al. Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin. Genet. 2003;64(4):339–349. DOI: 10.1034/j.13990004.2003.00151.x.Erdmann J., Daehmlow S., Wischke S., Senyuva M., Werner U., Raible J. et al. Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin. Genet. 2003;64(4):339–349. DOI: 10.1034/j.13990004.2003.00151.x.Van Driest S.L., Vasile V.C., Ommen S.R., Will M.L., Tajik A.J., Gersh B.J. et al. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 2004;44(9):1903–1910. DOI: 10.1016/j.jacc.2004.07.045.Van Driest S.L., Vasile V.C., Ommen S.R., Will M.L., Tajik A.J., Gersh B.J. et al. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 2004;44(9):1903–1910. DOI: 10.1016/j.jacc.2004.07.045.Alfares A.A., Kelly M.A., McDermott G., Funke B.H., Lebo M.S., Baxter S.B. et al. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet. Med. 2015;17(11):880–888. DOI: 10.1038/gim.2014.205.Alfares A.A., Kelly M.A., McDermott G., Funke B.H., Lebo M.S., Baxter S.B. et al. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet. Med. 2015;17(11):880–888. DOI: 10.1038/gim.2014.205.Liu W., Liu W., Hu D., Zhu T., Ma Z., Yang J. et al. Mutation spectrum in a large cohort of unrelated Chinese patients with hypertrophic cardiomyopathy. Am. J. Cardiol. 2013;112(4):585–589. DOI: 10.1016/j.amjcard.2013.04.021.Liu W., Liu W., Hu D., Zhu T., Ma Z., Yang J. et al. Mutation spectrum in a large cohort of unrelated Chinese patients with hypertrophic cardiomyopathy. Am. J. Cardiol. 2013;112(4):585–589. DOI: 10.1016/j.amjcard.2013.04.021.Harper A.R., Goel A., Grace C., Thomson K.L., Petersen S.E., Xu X. et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. Nat. Genet. 2021;53(2):135–142. DOI: 10.1038/s41588-020-00764-0.Harper A.R., Goel A., Grace C., Thomson K.L., Petersen S.E., Xu X. et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. Nat. Genet. 2021;53(2):135–142. DOI: 10.1038/s41588-020-00764-0.Cirino A.L., Lakdawala N.K., McDonough B., Conner L., Adler D., Weinfeld M. et al. A Comparison of whole genome sequencing to multigene panel testing in hypertrophic cardiomyopathy patients. Circ. Cardiovasc. Genet. 2017;10(5):e001768. DOI: 10.1161/CIRCGENETICS.117.001768.Cirino A.L., Lakdawala N.K., McDonough B., Conner L., Adler D., Weinfeld M. et al. A Comparison of whole genome sequencing to multigene panel testing in hypertrophic cardiomyopathy patients. Circ. Cardiovasc. Genet. 2017;10(5):e001768. DOI: 10.1161/CIRCGENETICS.117.001768.Дземешкевич С.Л., Мотрева А.П., Калмыкова О.В., Мартьянова Ю.Б., Синицын В.Е., Мершина Е.А. и др. Гипертрофическая кардиомиопатия у молодых: фенотип, генотип и варианты лечебной тактики. Клиническая и экспериментальная хирургия. Журнал имени академика Б.В. Петровского. 2019;7(3):54–62. DOI: 10.24411/2308-1198-2019-13006.Дземешкевич С.Л., Мотрева А.П., Калмыкова О.В., Мартьянова Ю.Б., Синицын В.Е., Мершина Е.А. и др. Гипертрофическая кардиомиопатия у молодых: фенотип, генотип и варианты лечебной тактики. Клиническая и экспериментальная хирургия. Журнал имени академика Б.В. Петровского. 2019;7(3):54–62. DOI: 10.24411/2308-1198-2019-13006.Wang B., Wang J., Wang L.F., Yang F., Xu L., Li W.X. et al. Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy. Mol. Med. Rep. 2019;20(6):5229–5238. DOI: 10.3892/mmr.2019.10754.Wang B., Wang J., Wang L.F., Yang F., Xu L., Li W.X. et al. Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy. Mol. Med. Rep. 2019;20(6):5229–5238. DOI: 10.3892/mmr.2019.10754.Coto E., Reguero J.R., Palacín M., Gómez J., Alonso B., Iglesias S. et al. Resequencing the whole MYH7 gene (including the intronic, promoter, and 3’ UTR sequences) in hypertrophic cardiomyopathy. J. Mol. Diagn. 2012;14(5):518–524. DOI: 10.1016/j.jmoldx.2012.04.001.Coto E., Reguero J.R., Palacín M., Gómez J., Alonso B., Iglesias S. et al. Resequencing the whole MYH7 gene (including the intronic, promoter, and 3’ UTR sequences) in hypertrophic cardiomyopathy. J. Mol. Diagn. 2012;14(5):518–524. DOI: 10.1016/j.jmoldx.2012.04.001.Puckelwartz M.J., Pesce L.L., Dellefave-Castillo L.M., Wheeler M.T., Pottinger T.D., Robinson A.C. et al. Genomic context differs between human dilated cardiomyopathy and hypertrophic cardiomyopathy. J. Am. Heart Assoc. 2021;10(7):e019944. DOI: 10.1161/JAHA.120.019944.Puckelwartz M.J., Pesce L.L., Dellefave-Castillo L.M., Wheeler M.T., Pottinger T.D., Robinson A.C. et al. Genomic context differs between human dilated cardiomyopathy and hypertrophic cardiomyopathy. J. Am. Heart Assoc. 2021;10(7):e019944. DOI: 10.1161/JAHA.120.019944.Xu F., Chen Y., Tillman K.A., Cui Y., Williams R.W., Bhattacharya S.K. et al. Characterizing modifier genes of cardiac fibrosis phenotype in hypertrophic cardiomyopathy. Int. J. Cardiol. 2021;330:135–141. DOI: 10.1016/j.ijcard.2021.01.047.Xu F., Chen Y., Tillman K.A., Cui Y., Williams R.W., Bhattacharya S.K. et al. Characterizing modifier genes of cardiac fibrosis phenotype in hypertrophic cardiomyopathy. Int. J. Cardiol. 2021;330:135–141. DOI: 10.1016/j.ijcard.2021.01.047.Pieles G.E., Alkon J., Manlhiot C., Fan C.S., Kinnear C., Benson L.N. et al. Association between genetic variants in the HIF1A-VEGF pathway and left ventricular regional myocardial deformation in patients with hypertrophic cardiomyopathy. Pediatr. Res. 2021;89(3):628–635. DOI: 10.1038/s41390020-0929-z.Pieles G.E., Alkon J., Manlhiot C., Fan C.S., Kinnear C., Benson L.N. et al. Association between genetic variants in the HIF1A-VEGF pathway and left ventricular regional myocardial deformation in patients with hypertrophic cardiomyopathy. Pediatr. Res. 2021;89(3):628–635. DOI: 10.1038/s41390020-0929-z.Чакова Н.Н., Комиссарова С.М., Ниязова С.С. Мутации в генах ионных каналов при гипертрофической кардиомиопатии. Клиническая и экспериментальная хирургия. Журнал имени академика Б.В. Петровского. 2019;7(3):63–69. DOI: 10.24411/2308-1198-2019-13007.Чакова Н.Н., Комиссарова С.М., Ниязова С.С. Мутации в генах ионных каналов при гипертрофической кардиомиопатии. Клиническая и экспериментальная хирургия. Журнал имени академика Б.В. Петровского. 2019;7(3):63–69. DOI: 10.24411/2308-1198-2019-13007.Repetti G.G., Kim Y., Pereira A.C., Ingles J., Russell M.W., Lakdawala N.K. et al. Discordant clinical features of identical hypertrophic cardiomyopathy twins. Proc. Natl. Acad. Sci. U S A. 2021;118(10):e2021717118. DOI: 10.1073/pnas.2021717118.Repetti G.G., Kim Y., Pereira A.C., Ingles J., Russell M.W., Lakdawala N.K. et al. Discordant clinical features of identical hypertrophic cardiomyopathy twins. Proc. Natl. Acad. Sci. U S A. 2021;118(10):e2021717118. DOI: 10.1073/pnas.2021717118.Niimura H., Bachinski L.L., Sangwatanaroj S., Watkins H., Chudley A.E., McKenna W. et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N. Engl. J. Med. 1998;338(18):1248– 1257. DOI: 10.1056/NEJM199804303381802.Niimura H., Bachinski L.L., Sangwatanaroj S., Watkins H., Chudley A.E., McKenna W. et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N. Engl. J. Med. 1998;338(18):1248– 1257. DOI: 10.1056/NEJM199804303381802.Fananapazir L., Epstein N.D. Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations. Circulation. 1994;89(1):22– 32. DOI: 10.1161/01.cir.89.1.22.Fananapazir L., Epstein N.D. Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations. Circulation. 1994;89(1):22– 32. DOI: 10.1161/01.cir.89.1.22.Maron B.J., Mackey-Bojack S., Facile E., Duncanson E., Rowin E.J., Maron M.S. Hypertrophic cardiomyopathy and sudden death initially identified at autopsy. Am. J. Cardiol. 2020;127:139–141. DOI: 10.1016/j.amjcard.2020.04.021.Maron B.J., Mackey-Bojack S., Facile E., Duncanson E., Rowin E.J., Maron M.S. Hypertrophic cardiomyopathy and sudden death initially identified at autopsy. Am. J. Cardiol. 2020;127:139–141. DOI: 10.1016/j.amjcard.2020.04.021.Yogasundaram H., Alhumaid W., Dzwiniel T., Christian S., Oudit G.Y. Cardiomyopathies and genetic testing in heart failure: Role in defining phenotype-targeted approaches and management. Can. J. Cardiol. 2021;37(4):547–559. DOI: 10.1016/j.cjca.2021.01.016.Yogasundaram H., Alhumaid W., Dzwiniel T., Christian S., Oudit G.Y. Cardiomyopathies and genetic testing in heart failure: Role in defining phenotype-targeted approaches and management. Can. J. Cardiol. 2021;37(4):547–559. DOI: 10.1016/j.cjca.2021.01.016.Musunuru K., Hershberger R.E., Day S.M., Klinedinst N.J., Landstrom A.P., Parikh V.N. et al. Genetic Testing for Inherited Cardiovascular Diseases: A Scientific State ment From the American Heart Association. Circ. Ge nom. Precis. Med. 2020;13(4):e000067. DOI: 10.1161/HCG.0000000000000067.Musunuru K., Hershberger R.E., Day S.M., Klinedinst N.J., Landstrom A.P., Parikh V.N. et al. Genetic Testing for Inherited Cardiovascular Diseases: A Scientific State ment From the American Heart Association. Circ. Ge nom. Precis. Med. 2020;13(4):e000067. DOI: 10.1161/HCG.0000000000000067.Garcia-Pavia P., Vázquez M.E., Segovia J., Salas C., Avellana P., Gómez-Bueno M. et al. Genetic basis of end-stage hypertrophic cardiomyopathy. Eur. J. Heart Fail. 2011;13(11):1193– 1201. DOI: 10.1093/eurjhf/hfr110.Garcia-Pavia P., Vázquez M.E., Segovia J., Salas C., Avellana P., Gómez-Bueno M. et al. Genetic basis of end-stage hypertrophic cardiomyopathy. Eur. J. Heart Fail. 2011;13(11):1193– 1201. DOI: 10.1093/eurjhf/hfr110.

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