medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2025.12.42-50medgen-3347Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHХарактеристика варианта p.Ser358Leu в гене TMEM43 и его фенотипические проявления.Characteristics of the p.Ser358Leu Variant in the TMEM43 Gene and Its Phenotypic Manifestations.ЧаковаН. Н.ChakovaN. N.n.chakova@igc.byНиязоваС. С.NiyazovaS. S.КомиссароваС. М.KomissarovaS. M.ЕфимоваА. А.EfimovaA. A.РинейскаяН. М.RineiskaN. M.ДолматовичТ. В.DolmatovichT. V.Институт генетики и цитологии Национальной Академия Наук Беларуси 220072, г. Минск, ул. Академическая, д. 27БеларусьInstitute of Genetics and Cytology of Belarus National Academy of SciencesBelarusРеспубликанский научно-практический центр «Кардиология» 220036, г. Минск, ул. Розы Люксембург, д. 110ББеларусьState Institution Republican Scientific and Practical Centre “Cardiology”BelarusРеспубликанский научно-практический центр «Кардиология» 220036, г. Минск, ул. Розы Люксембург, д. 110ББеларусьInstitute of Genetics and Cytology of Belarus National Academy of SciencesBelarusИнститут генетики и цитологии Национальной Академия Наук Беларуси 220072, г. Минск, ул. Академическая, д. 27БеларусьState Institution Republican Scientific and Practical Centre “Cardiology”Belarus20253101202624124250Copyright © Чакова Н.Н., Ниязова С.С., Комиссарова С.М., Ефимова А.А., Ринейская Н.М., Долматович Т.В., 20262026Чакова Н.Н., Ниязова С.С., Комиссарова С.М., Ефимова А.А., Ринейская Н.М., Долматович Т.В.Chakova N.N., Niyazova S.S., Komissarova S.M., Efimova A.A., Rineiska N.M., Dolmatovich T.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3347

Введение. Вариант c.1073C>T (p.Ser358Leu, rs63750743) в гене TMEM43 приводит к редкой форме аритмогенной кардиомиопатии 5-го типа (АКМП5), характеризующейся существенной жировой инфильтрацией миокарда, нарушением электрической проводимости и высоким риском внезапной сердечной смерти (ВСС), которая часто бывает первым проявлением заболевания. Цель: представить клиническое наблюдение пациентки с вариантом p.Ser358Leu и предварительным диагнозом идиопатическая желудочковая тахикардия (ИЖТ), измененным в ходе обследования на бивентрикулярный вариант АКМП, а также описать спектр фенотипических проявлений p.Ser358Leu у других носителей варианта. Методы. Представлены данные пробанда (пациентка, 65 лет) с диагнозом аритмогенная кардиомиопатия бивентрикулярная форма с рецидивирующей пароксизмальной устойчивой желудочковой тахикардией (ЖТ) и синкопальными состояниями. Клиническое обследование включало ЭКГ в 12 отведениях, ЭхоКГ, МРТ сердца с отсроченным контрастированием, суточное мониторирование ЭКГ (СМ ЭКГ) и коронароангиографию. Генетическое исследование выполнялось методом высокопроизводительного секвенирования (NGS) с использованием панели из 174 генов, ассоциированных с наследственными сердечно-сосудистыми заболеваниями. В семейном анамнезе пациентки были три случая внезапной смерти родственников мужского пола. Результаты. При обследовании в РНПЦ «Кардиология» по данным ЭКГ зарегистрированы регресс зубцов R в отведениях V1-V3, отрицательные зубцы Т в III и AVF отведениях. При СМ ЭКГ зарегистрированы одиночные и парные желудочковые экстрасистолы, одиночные суправентрикулярные экстрасистолы и эпизод идиовентрикулярного ритма. Анализ данных МРТ сердца выявил морфофункциональные аномалии, соответствующие МРТ-картине бивентрикулярного варианта АКМП согласно Падуанским критериям, 2020 г. Учитывая наличие гемодинамически значимых пароксизмов ЖТ пациентке имплантирован однокамерный кардиовертер-дефибриллятор. При генетическом исследовании обнаружен патогенный вариант c.1073C>T (p.Ser358Leu, rs63750743) в гене TMEM43. Выводы. Патогенный вариант p.Ser358Leu в гене TMEM43 имеет различия в фенотипическом проявлении, однако чаще характеризуется как злокачественная нуклеотидная замена, ассоциированная с ранним развитием АКМП и высоким риском ВСС, особенно у лиц мужского пола. Рассмотренный клинический случай подтверждает высокий риск ВСС у носителей варианта p.Ser358Leu в гене TMEM43 и демонстрирует трудности обнаружения структурных изменений миокарда у его обладателей. Исходя из этого, анализ на носительство мутации p.Ser358Leu в гене TMEM43 следует включить в генетическое тестирование не только пациентам с АКМП, но и лицам с идиопатической ЖТ при отсутствии вариантов в генах, ассоциированных с каналопатиями.

Introduction. The c.1073C>T (p.Ser358Leu, rs63750743) variant in the TMEM43 gene causes a rare form of arrhythmogenic cardiomyopathy type 5 (ACM5), characterized by significant fatty infiltration of the myocardium, electrical conduction abnormalities, and a high risk of sudden cardiac death (SCD) – often the first manifestation of the disease. Objective: to present the clinical case of a female patient with the p.Ser358Leu variant, initially diagnosed with idiopathic ventricular tachycardia (IVT), later reclassified as biventricular arrhythmogenic cardiomyopathy (ACM); and to describe the spectrum of phenotypic manifestations of p.Ser358Leu in other carriers. Methods. A 65-year-old female patient experienced recurrent sustained ventricular tachycardia (VT). Clinical work-up included 12-lead ECG, transthoracic echocardiogram (TTE), cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE), 24-hour ECG monitoring, and coronary angiography. Genetic analysis was performed using next-generation sequencing (NGS) of a panel of 174 genes linked to inherited cardiovascular diseases. There was a family history of three male relatives who died suddenly. Results. ECG showed sinus bradycardia, reduced R-wave amplitude in V1–V3, and T-wave inversions in leads III and aVF. Holter ECG revealed isolated and paired ventricular extrasystoles, single supraventricular extrasystoles, and an episode of idioventricular rhythm. Cardiac MRI demonstrated morpho-functional abnormalities consistent with the biventricular form of ACM per the 2020 Padua criteria. Due to hemodynamically significant VT, a cardioverter-defibrillator (ICD) was implanted. The was detected in the TMEM43 gene. The pathogenic variant c.1073C>T (p.Ser358Leu, rs63750743) in TMEM43 gene was detected. Conclusion. The pathogenic p.Ser358Leu variant in TMEM43 exhibits variable phenotypic expression but is most often considered a malignant nucleotide substitution, associated with early-onset ACM and high SCD risk, especially in males. This case confirms the very high risk of SCD in p.Ser358Leu carriers and highlights the difficulty of detecting myocardial structural changes in such individuals. Therefore, screening for the p.Ser358Leu TMEM43 mutation should be included not only in patients with ACM, but also in individuals with IVT when no pathogenic variants are found in channelopathy-associated genes.

аритмогенная кардиомиопатия правого желудочкавариант p.Ser358Leuген TMEM43фенотипические проявлениявнезапная сердечная смертьarrhythmogenic right ventricular cardiomyopathyp.Ser358Leu variantTMEM43 genephenotypic manifestationssudden cardiac deathРабота выполнена в рамках проекта 17(18) «Разработать и внедрить метод оценки риска внезапной сердечной смерти у пациентов с идиопатическими желудочковыми тахикардиями с использованием технологии высокопроизводительного секвенирования» подпрограммы 1 «Инновационные биотехнологии» ГП «Наукоемкие технологии и техника», 2021-2025 годы.The work was carried out within the framework of project No. 17 (18) of subprogram 1 “Innovative biotechnologies” of the State Program “Science-intensive technologies and engineering”, 2021-2025.ReferencesJames C.A., Jongbloed J.D.H., Hershberger R.E. et al. International evidence based reappraisal of genes associated with arrhythmogenic right ventricular cardiomyopathy using the clinical genome resource framework. Circ. Genomic Precis. Med. 2021;14(3):E003273. doi:10.1161/CIRCGEN.120.003273.James C.A., Jongbloed J.D.H., Hershberger R.E. et al. International evidence based reappraisal of genes associated with arrhythmogenic right ventricular cardiomyopathy using the clinical genome resource framework. Circ. Genomic Precis. Med. 2021;14(3):E003273. doi:10.1161/CIRCGEN.120.003273.Alcalde M., Campuzano O., Berne P. et al. Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy. PLoS One. 2014;9(6):e100560. doi: 10.1371/journal.pone.0100560.Alcalde M., Campuzano O., Berne P. et al. Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy. PLoS One. 2014;9(6):e100560. doi: 10.1371/journal.pone.0100560.Akdis D., Brunckhorst C., Duru F. et al. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes. Arrhythm. Electrophysiol. Rev. 2016;5(2):90-101. doi: 10.15420/AER.2016.4.3.Akdis D., Brunckhorst C., Duru F. et al. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes. Arrhythm. Electrophysiol. Rev. 2016;5(2):90-101. doi: 10.15420/AER.2016.4.3.Bengtsson L., Otto H. LUMA interacts with emerin and influences its distribution at the inner nuclear membrane. J. Cell Sci. 2008;121(Pt 4):536-48. doi: 10.1242/jcs.019281.Bengtsson L., Otto H. LUMA interacts with emerin and influences its distribution at the inner nuclear membrane. J. Cell Sci. 2008;121(Pt 4):536-48. doi: 10.1242/jcs.019281.Jiang C., Zhu Y., Zhou Z. et al. TMEM43/LUMA is a key signaling component mediating EGFR-induced NF-kappaB activation and tumor progression. Oncogene. 2017;36:2813-2823. doi: 10.1038/onc.2016.430.Jiang C., Zhu Y., Zhou Z. et al. TMEM43/LUMA is a key signaling component mediating EGFR-induced NF-kappaB activation and tumor progression. Oncogene. 2017;36:2813-2823. doi: 10.1038/onc.2016.430.Li J., Song Y., Zhang C. et al. TMEM43 promotes pancreatic cancer progression by stabilizing PRPF3 and regulating RAP2B/ERK axis. Cell. Mol. Biol. Lett. 2022;27(1):24. doi: 10.1186/s11658-022-00321-z.Li J., Song Y., Zhang C. et al. TMEM43 promotes pancreatic cancer progression by stabilizing PRPF3 and regulating RAP2B/ERK axis. Cell. Mol. Biol. Lett. 2022;27(1):24. doi: 10.1186/s11658-022-00321-z.Jang M. W., Oh D.Y., Yi E. et al. A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder. Proc. Natl. Acad. Sci. 2021;118(22):e2019681118. doi: 10.1073/pnas.2019681118.Jang M. W., Oh D.Y., Yi E. et al. A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder. Proc. Natl. Acad. Sci. 2021;118(22):e2019681118. doi: 10.1073/pnas.2019681118.Landrum M. J., Lee J. M., Benson M. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46(D1):D1062–D1067. doi: 10.1093/nar/gkx1153.Landrum M. J., Lee J. M., Benson M. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46(D1):D1062–D1067. doi: 10.1093/nar/gkx1153.Aalbæk Kjærgaard K., Kristensen J., Mølgaard H. et al. Failure of ICD therapy in lethal arrhythmogenic right ventricular cardiomyopathy type 5 caused by the TMEM43 p.Ser358Leu mutation. HeartRhythm. Case Rep. 2016;2(3):217-222. doi: 10.1016/j.hrcr.2015.12.009.Aalbæk Kjærgaard K., Kristensen J., Mølgaard H. et al. Failure of ICD therapy in lethal arrhythmogenic right ventricular cardiomyopathy type 5 caused by the TMEM43 p.Ser358Leu mutation. HeartRhythm. Case Rep. 2016;2(3):217-222. doi: 10.1016/j.hrcr.2015.12.009.Wang K., Li M., Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164. doi: 10.1093/nar/gkq603.Wang K., Li M., Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164. doi: 10.1093/nar/gkq603.Adzhubei I.A., Schmidt S., Peshkin L. et al. A method and server for predicting damaging missense mutations. Nat. Methods. 2010;7(4):248-9. doi: 10.1038/nmeth0410-248.Adzhubei I.A., Schmidt S., Peshkin L. et al. A method and server for predicting damaging missense mutations. Nat. Methods. 2010;7(4):248-9. doi: 10.1038/nmeth0410-248.Kumar P., Henikoff S., Ng P.C. Predicting the effects of coding nonsynonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073-81. doi: 10.1038/nprot.2009.86.Kumar P., Henikoff S., Ng P.C. Predicting the effects of coding nonsynonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073-81. doi: 10.1038/nprot.2009.86.Shihab H.A., Gough J., Cooper D.N. et al. Predicting the functional, molecular and phenotypic consequences of amino acid substitutions using hidden markov models. Hum. Mutat. 2013;34(1):57-65. doi: 10.1002/humu.22225.Shihab H.A., Gough J., Cooper D.N. et al. Predicting the functional, molecular and phenotypic consequences of amino acid substitutions using hidden markov models. Hum. Mutat. 2013;34(1):57-65. doi: 10.1002/humu.22225.Schwarz J.M., Rödelsperger C., Schuelke M.et al. MutationTaster evaluates disease-causing potential of sequence alterations. Nat. Methods. 2010;7(8):575-6. doi: 10.1038/nmeth0810-575.Schwarz J.M., Rödelsperger C., Schuelke M.et al. MutationTaster evaluates disease-causing potential of sequence alterations. Nat. Methods. 2010;7(8):575-6. doi: 10.1038/nmeth0810-575.Hodgkinson K.A., Connors S.P., Merner N.et al. The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43. Clin. Genet. 2013;83(4):321-31. doi: 10.1111/j.1399-0004.2012.01919.x.Hodgkinson K.A., Connors S.P., Merner N.et al. The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43. Clin. Genet. 2013;83(4):321-31. doi: 10.1111/j.1399-0004.2012.01919.x.Hodgkinson K.A., Howes A.J., Boland P. et al. Long-term clinical outcome of arrhythmogenic right ventricular cardiomyopathy in individuals with a p.S358L mutation in TMEM43 following implantable cardioverter defibrillator therapy. Circ. Arrhythm. Electrophysiol. 2016;9(3):e003589. doi: 10.1161/CIRCEP.115.003589.Hodgkinson K.A., Howes A.J., Boland P. et al. Long-term clinical outcome of arrhythmogenic right ventricular cardiomyopathy in individuals with a p.S358L mutation in TMEM43 following implantable cardioverter defibrillator therapy. Circ. Arrhythm. Electrophysiol. 2016;9(3):e003589. doi: 10.1161/CIRCEP.115.003589.Dominguez F., Zorio E., Jimenez-Jaimez J. et al. Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. Heart Rhythm. 2020;17(6):945-954. doi: 10.1016/j.hrthm.2020.01.035.Dominguez F., Zorio E., Jimenez-Jaimez J. et al. Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. Heart Rhythm. 2020;17(6):945-954. doi: 10.1016/j.hrthm.2020.01.035.Merner N.D., Hodgkinson K.A., Haywood A.F. et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am. J. Hum. Genet. 2008;82(4):809-21. doi: 10.1016/j.ajhg.2008.01.010.Merner N.D., Hodgkinson K.A., Haywood A.F. et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am. J. Hum. Genet. 2008;82(4):809-21. doi: 10.1016/j.ajhg.2008.01.010.Milting H., Klauke B., Christensen A.H. et al. The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus. Eur. Heart J. 2015;36(14):872-81. doi: 10.1093/eurheartj/ehu077.Milting H., Klauke B., Christensen A.H. et al. The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus. Eur. Heart J. 2015;36(14):872-81. doi: 10.1093/eurheartj/ehu077.Haywood A.F., Merner N.D., Hodgkinson K.A. et al. Recurrent missense mutations in TMEM43 (ARVD5) due to founder effects cause arrhythmogenic cardiomyopathies in the UK and Canada. Eur. Heart J. 2013;34(13):1002-11. doi: 10.1093/eurheartj/ehs383.Haywood A.F., Merner N.D., Hodgkinson K.A. et al. Recurrent missense mutations in TMEM43 (ARVD5) due to founder effects cause arrhythmogenic cardiomyopathies in the UK and Canada. Eur. Heart J. 2013;34(13):1002-11. doi: 10.1093/eurheartj/ehs383.Baskin B., Skinner J.R., Sanatani S. et al. TMEM43 mutations associated with arrhythmogenic right ventricular cardiomyopathy in non-Newfoundland populations. Hum. Genet. 2013;132(11):1245 52. doi: 10.1007/s00439-013-1323-2.Baskin B., Skinner J.R., Sanatani S. et al. TMEM43 mutations associated with arrhythmogenic right ventricular cardiomyopathy in non-Newfoundland populations. Hum. Genet. 2013;132(11):1245 52. doi: 10.1007/s00439-013-1323-2.Ramensky V.E., Ershova A.I., Zaicenoka M. et al. Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region. Front Genet. 2021;12:709419. doi: 10.3389/fgene.2021.709419Ramensky V.E., Ershova A.I., Zaicenoka M. et al. Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region. Front Genet. 2021;12:709419. doi: 10.3389/fgene.2021.709419Siragam V., Cui X., Masse S. et al., TMEM43 mutation p.S358L alters intercalated disc protein expression and reduces conduction velocity in arrhythmogenic right ventricular cardiomyopathy. PLoS One. 2014;9(10):e109128. doi: 10.1371/journal.pone.0109128.Siragam V., Cui X., Masse S. et al., TMEM43 mutation p.S358L alters intercalated disc protein expression and reduces conduction velocity in arrhythmogenic right ventricular cardiomyopathy. PLoS One. 2014;9(10):e109128. doi: 10.1371/journal.pone.0109128.Christensen A.H., Andersen C.B., Tybjaerg-Hansen A. et al. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. Clin. Genet. 2011;80(3):256-64. doi: 10.1111/j.1399-0004.2011.01623.x.Christensen A.H., Andersen C.B., Tybjaerg-Hansen A. et al. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. Clin. Genet. 2011;80(3):256-64. doi: 10.1111/j.1399-0004.2011.01623.x.Vasireddi S.K., Sattayaprasert P., Yang D. et al. Adipogenic signaling promotes arrhythmia substrates before structural abnormalities in TMEM43 ARVC. J. Pers. Med. 2022;12(10):1680. doi: 10.3390/jpm12101680.Vasireddi S.K., Sattayaprasert P., Yang D. et al. Adipogenic signaling promotes arrhythmia substrates before structural abnormalities in TMEM43 ARVC. J. Pers. Med. 2022;12(10):1680. doi: 10.3390/jpm12101680.Zheng G., Jiang C., Li Y. et al. TMEM43-S358L mutation enhances NF-κB-TGFβ signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Protein Cell. 2019;10(2):104-119. doi: 10.1007/s13238-018-0563-2.Zheng G., Jiang C., Li Y. et al. TMEM43-S358L mutation enhances NF-κB-TGFβ signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Protein Cell. 2019;10(2):104-119. doi: 10.1007/s13238-018-0563-2.Orgil B.O., Munkhsaikhan U., Pierre J.F. et al. The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model. Am. J. Physiol. Heart Circ. Physiol. 2023;324(6):H866-H880. doi: 10.1152/ajpheart.00712.2022.Orgil B.O., Munkhsaikhan U., Pierre J.F. et al. The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model. Am. J. Physiol. Heart Circ. Physiol. 2023;324(6):H866-H880. doi: 10.1152/ajpheart.00712.2022.Padrón-Barthe L., Villalba-Orero M., Gómez-Salinero J.M. et al. Severe cardiac dysfunction and death caused by arrhythmogenic right ventricular cardiomyopathy type 5 are improved by inhibition of glycogen synthase kinase-3β. Circulation. 2019;140(14):1188-1204. doi: 10.1161/CIRCULATIONAHA.119.040366.Padrón-Barthe L., Villalba-Orero M., Gómez-Salinero J.M. et al. Severe cardiac dysfunction and death caused by arrhythmogenic right ventricular cardiomyopathy type 5 are improved by inhibition of glycogen synthase kinase-3β. Circulation. 2019;140(14):1188-1204. doi: 10.1161/CIRCULATIONAHA.119.040366.Shinomiya H., Kato H., Kuramoto Y. et al. Aberrant accumulation of TMEM43 accompanied by perturbed transmural gene expression in arrhythmogenic cardiomyopathy. FASEB J. 2021;35(11):e21994. doi: 10.1096/fj.202100800R.Shinomiya H., Kato H., Kuramoto Y. et al. Aberrant accumulation of TMEM43 accompanied by perturbed transmural gene expression in arrhythmogenic cardiomyopathy. FASEB J. 2021;35(11):e21994. doi: 10.1096/fj.202100800R.Kang H., Lee C.J. Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles. Exp. Mol. Med. 2024;56(4):850-860. doi: 10.1038/s12276-024-01206-1.Kang H., Lee C.J. Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles. Exp. Mol. Med. 2024;56(4):850-860. doi: 10.1038/s12276-024-01206-1.Arbelo E., Protonotarios A., Gimeno J.R.et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur. Heart J. 2023;44(37):3503-3626. doi: 10.1093/eurheartj/ehad194.Arbelo E., Protonotarios A., Gimeno J.R.et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur. Heart J. 2023;44(37):3503-3626. doi: 10.1093/eurheartj/ehad194.Marcus F.I., McKenna W.J., Sherrill D. et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur. Heart J. 2010;31(7):806 14. doi: 10.1093/eurheartj/ehq025.Marcus F.I., McKenna W.J., Sherrill D. et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur. Heart J. 2010;31(7):806 14. doi: 10.1093/eurheartj/ehq025.Lalaguna L., Arévalo-Núñez de Arenas M., López-Olañeta M. et al. Overexpression of wild-type TMEM43 improves cardiac function in arrhythmogenic right ventricular cardiomyopathy type 5. Circ. Res. 2025;136(8):830-844. doi: 10.1161/CIRCRESAHA.124.325848.Lalaguna L., Arévalo-Núñez de Arenas M., López-Olañeta M. et al. Overexpression of wild-type TMEM43 improves cardiac function in arrhythmogenic right ventricular cardiomyopathy type 5. Circ. Res. 2025;136(8):830-844. doi: 10.1161/CIRCRESAHA.124.325848.

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