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Campo DCValorIdioma
dc.creatorCosta, Lucas Cadete Caldeira-
dc.date.accessioned2026-02-04T18:43:41Z-
dc.date.available2026-02-04T18:43:41Z-
dc.date.issued2025-12-12-
dc.identifier.citationCostapt_BR
dc.identifier.urihttps://repositorio.ufba.br/handle/ri/43991-
dc.description.abstractHereditary cardiomyopathies represent a significant cause of sudden death in young individuals and constitute a public health concern due to their association with ventricular arrhythmias, progressive heart failure, and premature adverse outcomes. The MYBPC3 gene is the major contributor to hypertrophic cardiomyopathy and is also implicated in phenotypes of dilated cardiomyopathy and arrhythmic disorders, reflecting the broad spectrum of variants that impair the stability, structure, and function of the cMyBPC protein. Functional reduction of cMyBPC, arising from mechanisms of haploinsufficiency,typically mediated by truncating variants subject to transcript decay, but also by missense variants that disrupt folding, phosphorylation, or sarcomeric interactions,leads to myofibrillar disarray, cardiac remodeling, and fibrosis. In this study, we describe and characterize MYBPC3 variants identified in patients with cardiomyopathies classified as idiopathic who are followed at the Cardiology Service of Hospital Universitário Professor Edgard Santos and who underwent etiological investigation through next-generation sequencing.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal da Bahiapt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectCardiogenéticapt_BR
dc.subjectCardiomiopatia Hereditáriapt_BR
dc.subjectCardiomiopatia Hipertróficapt_BR
dc.subjectCardiomiopatia Sarcoméricapt_BR
dc.subjectMYBPC3pt_BR
dc.subject.otherCardiogeneticspt_BR
dc.subject.otherHereditary Cardiomyopathypt_BR
dc.subject.otherHypertrophic Cardiomyopathypt_BR
dc.subject.otherSarcomeric Cardiomyopathypt_BR
dc.subject.otherMYBPC3pt_BR
dc.titleCaracterização das Variantes no Gene MYBPC3 em Pacientes com Cardiomiopatias Hereditáriaspt_BR
dc.title.alternativeCharacterization of Variants in the MYBPC3 Gene in Patients with Hereditary Cardiomyopathiespt_BR
dc.typeTrabalho de Conclusão de Cursopt_BR
dc.publisher.initialsUFBApt_BR
dc.publisher.countryBrasilpt_BR
dc.subject.cnpqCNPQ::CIENCIAS DA SAUDEpt_BR
dc.contributor.advisor1Nascimento, Samuel Ulisses Chaves Nogueira do-
dc.contributor.referee1Magalhães, Luíz Pereira de-
dc.contributor.referee2Cruz, Patrícia Pontes-
dc.description.resumoCardiomiopatias hereditárias representam causa relevante de morte súbita em indivíduos jovens e constituem problema de saúde pública pela associação com arritmias ventriculares, insuficiência cardíaca progressiva e desfechos precoces. O gene MYBPC3 é o principal responsável por cardiomiopatia hipertrófica e também está implicado em fenótipos de cardiomiopatia dilatada e em distúrbios arrítmicos, refletindo a ampla distribuição de variantes que comprometem a estabilidade, a estrutura e a função da proteína cMyBPC. A redução funcional de cMyBPC, decorrente de mecanismos de haploinsuficiência, geralmente mediada por variantes truncantes sujeitas ao decaimento do transcrito, mas também por variantes missense que afetam dobramento, fosforilação ou interação sarcomérica, resulta em desorganização miofibrilar, remodelamento cardíaco e fibrose. Neste estudo, descrevemos e caracterizamos variantes identificadas em MYBPC3 em pacientes com cardiomiopatias consideradas idiopáticas acompanhados no Serviço de Cardiologia do Hospital Universitário Professor Edgard Santos, submetidos à investigação etiológica por meio de sequenciamento de nova geração.pt_BR
dc.publisher.departmentFaculdade de Medicina da Bahiapt_BR
dc.relation.references1.Sessa F, Esposito M, Messina G, Di Mizio G, Di Nunno N, Salerno M. Sudden death in adults: a practical flow chart for pathologist guidance. Healthcare. 2021;9(7):870. DOI: 10.3390/healthcare9070870 2.Deo R, Albert CM. Epidemiology and Genetics of Sudden Cardiac Death. Circulation. 2012;125(4):620–37. DOI: 10.1161/CIRCULATIONAHA.111.023838 3.Duong G, M. Helms T, A. Karle C. A multiplex PCR strategy to screen for known mutations in families with sudden cardiac death burden. JBM. 2017;4(3):1. DOI: 10.14440/jbm.2017.181 4.Kelishadi R, Poursafa P. A Review on the Genetic, Environmental, and Lifestyle Aspects of the Early-Life Origins of Cardiovascular Disease. Current Problems in Pediatric and Adolescent Health Care. 2014;44(3):54–72. DOI: 10.1016/j.cppeds.2013.12.005 5.McKenna WJ, Maron BJ, Thiene G. Classification, Epidemiology, and Global Burden of Cardiomyopathies. Circulation Research. 2017;121(7):722–30. DOI: 10.1161/CIRCRESAHA.117.309711 6.Judge DP. Use of Genetics in the Clinical Evaluation of Cardiomyopathy. JAMA. 2009;302(22):2471. DOI: 10.1001/jama.2009.1787 7.Akinrinade O, Lesurf R, Genomics England Research Consortium, Ambrose JC, Arumugam P, Bleda M, et al. Age and Sex Differences in the Genetics of Cardiomyopathy. J of Cardiovasc Trans Res. 2023;16(6):1287–302. DOI: 10.1007/s12265-023-10411-8 8.Carrington M, De Gouveia RH, Teixeira R, Corte-Real F, Gonçalves L, Providência R. Sudden death in young South European population: a cross-sectional study of postmortem cases. Sci Rep. 2023;13(1):22734. DOI: 10.1038/s41598-023-47502-0 9.Webster G, Puckelwartz MJ, Pesce LL, Dellefave-Castillo LM, Vanoye CG, Potet F, et al. Genomic Autopsy of Sudden Deaths in Young Individuals. JAMA Cardiol. 2021;6(11):1247. DOI: 10.1001/jamacardio.2021.2789 10.Bagnall RD, Weintraub RG, Ingles J, Duflou J, Yeates L, Lam L, et al. A Prospective Study of Sudden Cardiac Death among Children and Young Adults. N Engl J Med. 2016;374(25):2441–52. DOI: 10.1056/NEJMoa1510687 11.Daoud H, Ghani M, Nfonsam L, Potter R, Ordorica S, Haslett V, et al. Genetic Diagnostic Testing for Inherited Cardiomyopathies. The Journal of Molecular Diagnostics. 2019;21(3):437–48. DOI: 10.1016/j.jmoldx.2019.01.004 12.Bonaventura J, Norambuena P, Tomašov P, Jindrová D, Šedivá H, Jr MM, et al. The utility of the Mayo Score for predicting the yield of genetic testing in patients with hypertrophic cardiomyopathy. aoms. 2019;15(3):641–9. DOI: 10.5114/aoms.2018.78767 13.Agarwal A, Yousefzai R, Jan MF, Cho C, Shetabi K, Bush M, et al. Clinical Application of WHF-MOGE(S) Classification for Hypertrophic Cardiomyopathy. gh. 2015;10(3):209. DOI: 10.1016/j.gheart.2015.01.001 14.Maron BJ, Maron MS, Semsarian C. Genetics of Hypertrophic Cardiomyopathy After 20 Years. Journal of the American College of Cardiology. 2012;60(8):705–15. DOI: 10.1016/j.jacc.2012.02.068 15.Van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I. Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. Neth Heart J. 2019;27(6):304–9. DOI: 10.1007/s12471-019-1250-5 16.Hayashi T, Tanimoto K, Hirayama-Yamada K, Tsuda E, Ayusawa M, Nunoda S, et al. Genetic background of Japanese patients with pediatric hypertrophic and restrictive cardiomyopathy. J Hum Genet. 2018;63(9):989–96. DOI: 10.1038/s10038-018-0479-y 17.Chanavat V, Janin A, Millat G. A fast and cost-effective molecular diagnostic tool for genetic diseases involved in sudden cardiac death. Clinica Chimica Acta. 2016;453:80–5. DOI: 10.1016/j.cca.2015.12.011 18.Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, et al. New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet. 2013;21(9):918–28. DOI: 10.1038/ejhg.2012.283 19.Seidman CE, Seidman JG. Robbins J, Watkins H, organizadores. Identifying Sarcomere Gene Mutations in Hypertrophic Cardiomyopathy: A Personal History. Circulation Research. 2011;108(6):743–50. DOI: 10.1161/CIRCRESAHA.110.223834 20.Seidman JG, Seidman C. The Genetic Basis for Cardiomyopathy. Cell. 2001;104(4):557–67. DOI: 10.1016/S0092-8674(01)00242-2 21.Walsh R, Buchan R, Wilk A, John S, Felkin LE, Thomson KL, et al. Defining the genetic architecture of hypertrophic cardiomyopathy: re-evaluating the role of non-sarcomeric genes. Eur Heart J. 2017;ehw603. DOI: 10.1093/eurheartj/ehw603 22.Hershberger RE, Givertz MM, Ho CY, Judge DP, Kantor PF, McBride KL, et al. Genetic Evaluation of Cardiomyopathy—A Heart Failure Society of America Practice Guideline. Journal of Cardiac Failure. 2018;24(5):281–302. DOI: 10.1016/j.cardfail.2018.03.004 23.Tudurachi B-S, Zăvoi A, Leonte A, Țăpoi L, Ureche C, Bîrgoan SG, et al. An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy. IJMS. 2023;24(13):10510. DOI: 10.3390/ijms241310510 24.Chung M-W, Tsoutsman T, Semsarian C. Hypertrophic cardiomyopathy: from gene defect to clinical disease. Cell Res. 2003;13(1):9–20. DOI: 10.1038/sj.cr.7290146 25.Kimura A. Molecular basis of hereditary cardiomyopathy: abnormalities in calcium sensitivity, stretch response, stress response and beyond. J Hum Genet. 2010;55(2):81–90. DOI: 10.1038/jhg.2009.138 26.Catrina BI, Batar F, Baltat G, Bitea CI, Puia A, Stoia O, et al. A Family with Myh7 Mutation and Different Forms of Cardiomyopathies. Biomedicines. 2023;11(7):2065. DOI: 10.3390/biomedicines11072065 27.Marian AJ, Braunwald E. Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circulation Research. 2017;121(7):749–70. DOI: 10.1161/CIRCRESAHA.117.311059 28.De Frutos F, Ochoa JP, Navarro-Peñalver M, Baas A, Bjerre JV, Zorio E, et al. Natural History of MYH7-Related Dilated Cardiomyopathy. Journal of the American College of Cardiology. 2022;80(15):1447–61. DOI: 10.1016/j.jacc.2022.07.023 29.Wadelius C. The Heart of the Matter - New Insights into the Genetics of Cardiomyopathy. Scandinavian Cardiovascular Journal. 2000;34(6):547–547. DOI: 10.1080/140174300750064440 30.Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, et al. Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation. 2018;138(14):1387–98. DOI: 10.1161/CIRCULATIONAHA.117.033200 31.Husser D, Ueberham L, Jacob J, Heuer D, Riedel-Heller S, Walker J, et al. Kirchmair R, organizador. Prevalence of clinically apparent hypertrophic cardiomyopathy in Germany—An analysis of over 5 million patients. PLoS ONE. 2018;13(5):e0196612. DOI: 10.1371/journal.pone.0196612 32.Ishihara K, Kubota Y, Matsuda J, Imori Y, Tokita Y, Asai K, et al. Predictive Factors for Decreasing Left Ventricular Ejection Fraction and Progression to the Dilated Phase of Hypertrophic Cardiomyopathy. JCM. 2023;12(15):5137. DOI: 10.3390/jcm12155137 33.Zhang Y, Xie W, Dai Y, Wu Z, Lin Y, Yang M, et al. Influencing and prognostic factors of end‐stage hypertrophic cardiomyopathy. ESC Heart Failure. 2024;11(6):4028–37. DOI: 10.1002/ehf2.15010 34.Jia X, Xiang X, Yang K, Zhao S. Dilated phenotype of hypertrophic cardiomyopathy: cardiac magnetic resonance assessment and 9-year follow-up. Cardiovascular Diagnosis and Therapy. 2024;14(4):73134–734. DOI: 10.21037/cdt-24-160 35.Spillmann F, Kühl U, Van Linthout S, Dominguez F, Escher F, Schultheiss H, et al. Reversible transition from a hypertrophic to a dilated cardiomyopathy. ESC Heart Failure. 2016;3(2):138–42. DOI: 10.1002/ehf2.12072 36.Xiao Y, Yang K-Q, Yang Y-K, Liu Y-X, Tian T, Song L, et al. Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy. Chinese Medical Journal. 2015;128(11):1483–9. DOI: 10.4103/0366-6999.157656 37.Olivotto I, Cecchi F, Poggesi C, Yacoub MH. Patterns of Disease Progression in Hypertrophic Cardiomyopathy: An Individualized Approach to Clinical Staging. Circ: Heart Failure. 2012;5(4):535–46. DOI: 10.1161/CIRCHEARTFAILURE.112.967026 38.Biagini E, Coccolo F, Ferlito M, Perugini E, Rocchi G, Bacchi-Reggiani L, et al. Dilated-Hypokinetic Evolution of Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2005;46(8):1543–50. DOI: 10.1016/j.jacc.2005.04.062 39.Ingles J, Goldstein J, Thaxton C, Caleshu C, Corty EW, Crowley SB, et al. Evaluating the Clinical Validity of Hypertrophic Cardiomyopathy Genes. Circ: Genomic and Precision Medicine. 2019;12(2):e002460. DOI: 10.1161/CIRCGEN.119.002460 40.Hespe S, Waddell A, Asatryan B, Owens E, Thaxton C, Adduru M-L, et al. Genes Associated With Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2025;85(7):727–40. DOI: 10.1016/j.jacc.2024.12.010 41.Carrier L, Bonne G, Bahrend E, Yu B, Richard P, Niel F, et al. Organization and Sequence of Human Cardiac Myosin Binding Protein C Gene (MYBPC3) and Identification of Mutations Predicted to Produce Truncated Proteins in Familial Hypertrophic Cardiomyopathy. Circulation Research. 1997;80(3):427–34. DOI: 10.1161/01.res.0000435859.24609.b3 42.Carrier L, Mearini G, Stathopoulou K, Cuello F. Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology. Gene. 2015;573(2):188–97. DOI: 10.1016/j.gene.2015.09.008 43.Sadayappan S, De Tombe PP. Cardiac myosin binding protein-C: redefining its structure and function. Biophys Rev. 2012;4(2):93–106. DOI: 10.1007/s12551-012-0067-x 44.Ratti J, Rostkova E, Gautel M, Pfuhl M. Structure and Interactions of Myosin-binding Protein C Domain C0. Journal of Biological Chemistry. 2011;286(14):12650–8. DOI: 10.1074/jbc.M110.156646 45.Howarth JW, Ramisetti S, Nolan K, Sadayappan S, Rosevear PR. Structural Insight into Unique Cardiac Myosin-binding Protein-C Motif. Journal of Biological Chemistry. 2012;287(11):8254–62. DOI: 10.1074/jbc.M111.309591 46.Suay‐Corredera C, Alegre‐Cebollada J. The mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP‐C. FEBS Letters. 2022;596(6):703–46. DOI: 10.1002/1873-3468.14301 47.McNamara JW, Singh RR, Sadayappan S. Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin. Proc Natl Acad Sci USA. 2019;116(24):11731–6. DOI: 10.1073/pnas.1821660116 48.Kensler RW, Craig R, Moss RL. Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments. Proc Natl Acad Sci USA. 2017;114(8). DOI: 10.1073/pnas.1614020114 49.Nelson S, Beck-Previs S, Sadayappan S, Tong C, Warshaw DM. Myosin-binding protein C stabilizes, but is not the sole determinant of SRX myosin in cardiac muscle. Journal of General Physiology. 2023;155(4):e202213276. DOI: 10.1085/jgp.202213276 50.Anderson RL, Trivedi DV, Sarkar SS, Henze M, Ma W, Gong H, et al. Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers. Proc Natl Acad Sci USA. 2018;115(35). DOI: 10.1073/pnas.1809540115 51.Ponnam S, Kampourakis T. Microscale thermophoresis suggests a new model of regulation of cardiac myosin function via interaction with cardiac myosin-binding protein C. Journal of Biological Chemistry. 2022;298(1):101485. DOI: 10.1016/j.jbc.2021.101485 52.Mamidi R, Gresham KS, Li J, Stelzer JE. Cardiac myosin binding protein-C Ser302 phosphorylation regulates cardiac β-adrenergic reserve. Sci Adv. 2017;3(3):e1602445. DOI: 10.1126/sciadv.1602445 53.Wang L, Sadayappan S, Kawai M. Xu X, organizador. Cardiac Myosin Binding Protein C Phosphorylation Affects Cross-Bridge Cycle’s Elementary Steps in a Site-Specific Manner. PLoS ONE. 2014;9(11):e113417. DOI: 10.1371/journal.pone.0113417 54.Gresham KS, Mamidi R, Stelzer JE. The contribution of cardiac myosin binding protein‐c Ser282 phosphorylation to the rate of force generation and in vivo cardiac contractility. The Journal of Physiology. 2014;592(17):3747–65. DOI: 10.1113/jphysiol.2014.276022 55.Gresham KS, Stelzer JE. The contributions of cardiac myosin binding protein C and troponin I phosphorylation to β‐adrenergic enhancement of in vivo cardiac function. The Journal of Physiology. 2016;594(3):669–86. DOI: 10.1113/JP270959 56.Rosas PC, Liu Y, Abdalla MI, Thomas CM, Kidwell DT, Dusio GF, et al. Phosphorylation of Cardiac Myosin-Binding Protein-C Is a Critical Mediator of Diastolic Function. Circ: Heart Failure. 2015;8(3):582–94. DOI: 10.1161/CIRCHEARTFAILURE.114.001550 57.Tong CW, Wu X, Liu Y, Rosas PC, Sadayappan S, Hudmon A, et al. Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1 -Adrenergic Stimulation. Circ: Heart Failure. 2015;8(3):595–604. DOI: 10.1161/CIRCHEARTFAILURE.114.001585 58.Stathopoulou K, Wittig I, Heidler J, Piasecki A, Richter F, Diering S, et al. S ‐glutathiolation impairs phosphoregulation and function of cardiac myosin‐binding protein C in human heart failure. The FASEB Journal. 2016;30(5):1849–64. DOI: 10.1096/fj.201500048 59.Olivotto I, Girolami F, Sciagrà R, Ackerman MJ, Sotgia B, Bos JM, et al. Microvascular Function Is Selectively Impaired in Patients With Hypertrophic Cardiomyopathy and Sarcomere Myofilament Gene Mutations. Journal of the American College of Cardiology. 2011;58(8):839–48. DOI: 10.1016/j.jacc.2011.05.018 60.Miyazaki T. Calpain and Cardiometabolic Diseases. IJMS. 2023;24(23):16782. DOI: 10.3390/ijms242316782 61.Barefield DY, McNamara JW, Lynch TL, Kuster DWD, Govindan S, Haar L, et al. Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury. Journal of Molecular and Cellular Cardiology. 2019;129:236–46. DOI: 10.1016/j.yjmcc.2019.03.006 62.Martin TG, Kirk JA. Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere. Journal of Molecular and Cellular Cardiology. 2020;148:89–102. DOI: 10.1016/j.yjmcc.2020.08.018 63.Bahrudin U, Morisaki H, Morisaki T, Ninomiya H, Higaki K, Nanba E, et al. Ubiquitin-Proteasome System Impairment Caused by a Missense Cardiac Myosin-binding Protein C Mutation and Associated with Cardiac Dysfunction in Hypertrophic Cardiomyopathy. Journal of Molecular Biology. 2008;384(4):896–907. DOI: 10.1016/j.jmb.2008.09.070 64.Vignier N, Schlossarek S, Fraysse B, Mearini G, Krämer E, Pointu H, et al. Nonsense-Mediated mRNA Decay and Ubiquitin–Proteasome System Regulate Cardiac Myosin-Binding Protein C Mutant Levels in Cardiomyopathic Mice. Circulation Research. 2009;105(3):239–48. DOI: 10.1161/CIRCRESAHA.109.201251 65.Gilda JE, Gomes AV. Proteasome dysfunction in cardiomyopathies. The Journal of Physiology. 2017;595(12):4051–71. DOI: 10.1113/JP273607 66.Glazier AA, Hafeez N, Mellacheruvu D, Basrur V, Nesvizhskii AI, Lee LM, et al. HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C. JCI Insight. 2018;3(11):e99319. DOI: 10.1172/jci.insight.99319 67.Schlossarek S, Englmann DR, Sultan KR, Sauer M, Eschenhagen T, Carrier L. Defective proteolytic systems in Mybpc3-targeted mice with cardiac hypertrophy. Basic Res Cardiol. 2012;107(1):235. DOI: 10.1007/s00395-011-0235-3 68.Smelter DF, De Lange WJ, Cai W, Ge Y, Ralphe JC. The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6 FnIII domain stability. American Journal of Physiology-Heart and Circulatory Physiology. 2018;314(6):H1179–91. DOI: 10.1152/ajpheart.00686.2017 69.Carrier L, Mearini G, Stathopoulou K, Cuello F. Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology. Gene. 2015;573(2):188–97. DOI: 10.1016/j.gene.2015.09.008 70.Pioner JM, Vitale G, Steczina S, Langione M, Margara F, Santini L, et al. Slower Calcium Handling Balances Faster Cross-Bridge Cycling in Human MYBPC3 HCM. Circulation Research. 2023;132(5):628–44. DOI: 10.1161/CIRCRESAHA.122.321956 71.Zhang XL, De S, McIntosh LP, Paetzel M. Structural Characterization of the C3 Domain of Cardiac Myosin Binding Protein C and Its Hypertrophic Cardiomyopathy-Related R502W Mutant. Biochemistry. 2014;53(32):5332–42. DOI: 10.1021/bi500784g 72.Harper AR, Goel A, Grace C, Thomson KL, Petersen SE, Xu X, et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. Nat Genet. 2021;53(2):135–42. DOI: 10.1038/s41588-020-00764-0 73.Desai DA, Rao VJ, Jegga AG, Dhandapany PS, Sadayappan S. Heterogeneous Distribution of Genetic Mutations in Myosin Binding Protein-C Paralogs. Front Genet. 2022;13:896117. DOI: 10.3389/fgene.2022.896117 74.Alamo L, Ware JS, Pinto A, Gillilan RE, Seidman JG, Seidman CE, et al. Effects of myosin variants on interacting-heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes. eLife. 2017;6:e24634. DOI: 10.7554/eLife.24634 75.Hoh JFY. Developmental, physiologic and phylogenetic perspectives on the expression and regulation of myosin heavy chains in mammalian skeletal muscles. J Comp Physiol B. 2023;193(4):355–82. DOI: 10.1007/s00360-023-01499-0 76.Morck MM, Bhowmik D, Pathak D, Dawood A, Spudich J, Ruppel KM. Hypertrophic cardiomyopathy mutations in the pliant and light chain-binding regions of the lever arm of human β-cardiac myosin have divergent effects on myosin function. eLife. 2022;11:e76805. DOI: 10.7554/eLife.76805 77.Wessels MW, Herkert JC, Frohn-Mulder IM, Dalinghaus M, Van Den Wijngaard A, De Krijger RR, et al. Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects. Eur J Hum Genet. 2015;23(7):922–8. DOI: 10.1038/ejhg.2014.211 78.Kuster DWD, Govindan S, Springer TI, Martin JL, Finley NL, Sadayappan S. A Hypertrophic Cardiomyopathy-associated MYBPC3 Mutation Common in Populations of South Asian Descent Causes Contractile Dysfunction. Journal of Biological Chemistry. 2015;290(9):5855–67. DOI: 10.1074/jbc.M114.607911 79.Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine. 2015;17(5):405–24. DOI: 10.1038/gim.2015.30 80.Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–43. DOI: 10.1038/s41586-020-2308-7 81.Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, et al. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. The American Journal of Human Genetics. 2016;99(4):877–85. DOI: 10.1016/j.ajhg.2016.08.016 82.Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46(3):310–5. DOI: 10.1038/ng.2892 83.My I, Di Pasquale E. Genetic Cardiomyopathies: The Lesson Learned from hiPSCs. JCM. 2021;10(5):1149. DOI: 10.3390/jcm10051149 84.Brandão KO, Tabel VA, Atsma DE, Mummery CL, Davis RP. Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies. Disease Models & Mechanisms. 2017;10(9):1039–59. DOI: 10.1242/dmm.030320 85.Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, et al. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genetics in Medicine. 2017;19(2):192–203. DOI: 10.1038/gim.2016.90 86.Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, et al. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genetics in Medicine. 2015;17(11):880–8. DOI: 10.1038/gim.2014.205 87.Desai MY, Owens A, Geske JB, Wolski K, Naidu SS, Smedira NG, et al. Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy. Journal of the American College of Cardiology. 2022;80(2):95–108. DOI: 10.1016/j.jacc.2022.04.048 88.Coats CJ, Masri A, Barriales-Villa R, Abraham TP, Brinkley DM, Claggett BL, et al. Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial. European Heart Journal. 2024;45(42):4464–78. DOI: 10.1093/eurheartj/ehae590 89.Han JL, Entcheva E. Gene Modulation with CRISPR-based Tools in Human iPSC-Cardiomyocytes. Stem Cell Rev and Rep. 2023;19(4):886–905. DOI: 10.1007/s12015-023-10506-4 90.Yao B, Lei Z, Gonçalves MAFV, Sluijter JPG. Integrating Prime Editing and Cellular Reprogramming as Novel Strategies for Genetic Cardiac Disease Modeling and Treatment. Curr Cardiol Rep. 2024;26(11):1197–208. DOI: 10.1007/s11886-024-02118-2 91.Chai AC, Cui M, Chemello F, Li H, Chen K, Tan W, et al. Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nat Med. 2023;29(2):401–11. DOI: 10.1038/s41591-022-02176-5 92.Bezzerides VJ, Prondzynski M, Carrier L, Pu WT. Gene therapy for inherited arrhythmias. Cardiovascular Research. 2020;116(9):1635–50. DOI: 10.1093/cvr/cvaa107 93.Gedicke‐Hornung C, Behrens‐Gawlik V, Reischmann S, Geertz B, Stimpel D, Weinberger F, et al. Rescue of cardiomyopathy through U7sn RNA ‐mediated exon skipping in Mybpc3 ‐targeted knock‐in mice. EMBO Mol Med. 2013;5(7):1128–45. DOI: 10.1002/emmm.201202168 94.Mearini G, Stimpel D, Krämer E, Geertz B, Braren I, Gedicke-Hornung C, et al. Repair of Mybpc3 mRNA by 5′-trans-splicing in a Mouse Model of Hypertrophic Cardiomyopathy. Molecular Therapy - Nucleic Acids. 2013;2:e102. DOI: 10.1038/mtna.2013.31 95.Zhang H, Zhan Q, Huang B, Wang Y, Wang X. AAV-mediated gene therapy: Advancing cardiovascular disease treatment. Front Cardiovasc Med. 2022;9:952755. DOI: 10.3389/fcvm.2022.952755 96.Greer-Short A, Greenwood A, Leon EC, Qureshi TN, Von Kraut K, Wong J, et al. AAV9-mediated MYBPC3 gene therapy with optimized expression cassette enhances cardiac function and survival in MYBPC3 cardiomyopathy models. Nat Commun. 2025;16(1):2196. DOI: 10.1038/s41467-025-57481-7 97.Arimura T, Bos JM, Sato A, Kubo T, Okamoto H, Nishi H, et al. Cardiac Ankyrin Repeat Protein Gene (ANKRD1) Mutations in Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2009;54(4):334–42. DOI: 10.1016/j.jacc.2008.12.082 98.Gómez J, Lorca R, Reguero JR, Morís C, Martín M, Tranche S, et al. Screening of the Filamin C Gene in a Large Cohort of Hypertrophic Cardiomyopathy Patients. Circ Cardiovasc Genet. 2017;10(2):e001584. DOI: 10.1161/CIRCGENETICS.116.001584 99.Lopes LR, Garcia-Hernández S, Lorenzini M, Futema M, Chumakova O, Zateyshchikov D, et al. Alpha-protein kinase 3 ( ALPK3 ) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy. European Heart Journal. 2021;42(32):3063–73. DOI: 10.1093/eurheartj/ehab424 100.Ochoa JP, Sabater-Molina M, García-Pinilla JM, Mogensen J, Restrepo-Córdoba A, Palomino-Doza J, et al. Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2018;72(20):2457–67. DOI: 10.1016/j.jacc.2018.10.001 101.McNamara JW, Li A, Smith NJ, Lal S, Graham RM, Kooiker KB, et al. Ablation of cardiac myosin binding protein-C disrupts the super-relaxed state of myosin in murine cardiomyocytes. Journal of Molecular and Cellular Cardiology. 2016;94:65–71. DOI: 10.1016/j.yjmcc.2016.03.009 102.Nollet EE, Duursma I, Rozenbaum A, Eggelbusch M, Wüst RCI, Schoonvelde SAC, et al. Mitochondrial dysfunction in human hypertrophic cardiomyopathy is linked to cardiomyocyte architecture disruption and corrected by improving NADH-driven mitochondrial respiration. European Heart Journal. 2023;44(13):1170–85. DOI: 10.1093/eurheartj/ehad028 103.Ranjbarvaziri S, Kooiker KB, Ellenberger M, Fajardo G, Zhao M, Vander Roest AS, et al. Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy. Circulation. 2021;144(21):1714–31. DOI: 10.1161/CIRCULATIONAHA.121.053575 104.Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, et al. Sarcomere Protein Gene Mutations in Hypertrophic Cardiomyopathy of the Elderly. Circulation. 2002;105(4):446–51. DOI: 10.1161/hc0402.102990 105.Van Waning JI, Caliskan K, Hoedemaekers YM, Van Spaendonck-Zwarts KY, Baas AF, Boekholdt SM, et al. Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy. Journal of the American College of Cardiology. 2018;71(7):711–22. DOI: 10.1016/j.jacc.2017.12.019 106.Huang Z, Lin K, Huang J, Chen Y, Liu H, Zhang X, et al. Characteristics and outcomes associated with sarcomere mutations in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis. International Journal of Cardiology. 2024;409:132213. DOI: 10.1016/j.ijcard.2024.132213 107.Bonaventura J, Rowin EJ, Chan RH, Chin MT, Puchnerova V, Polakova E, et al. Relationship Between Genotype Status and Clinical Outcome in Hypertrophic Cardiomyopathy. JAHA. 2024;13(10):e033565. DOI: 10.1161/JAHA.123.033565 108.De Marvao A, McGurk KA, Zheng SL, Thanaj M, Bai W, Duan J, et al. Phenotypic Expression and Outcomes in Individuals With Rare Genetic Variants of Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology. 2021;78(11):1097–110. DOI: 10.1016/j.jacc.2021.07.017 109.Zhou N, Weng H, Zhao W, Tang L, Ge Z, Tian F, et al. Gene-echocardiography: refining genotype–phenotype correlations in hypertrophic cardiomyopathy. European Heart Journal - Cardiovascular Imaging. 2023;25(1):127–35. DOI: 10.1093/ehjci/jead200 110.Zou X, Ouyang H, Lin F, Zhang H, Yang Y, Pang D, et al. MYBPC3 deficiency in cardiac fibroblasts drives their activation and contributes to fibrosis. Cell Death Dis. 2022;13(11):948. DOI: 10.1038/s41419-022-05403-6 111.Watkins H, Rosenzweig A, Hwang D-S, Levi T, McKenna W, Seidman CE, et al. Characteristics and Prognostic Implications of Myosin Missense Mutations in Familial Hypertrophic Cardiomyopathy. N Engl J Med. 1992;326(17):1108–14. DOI: 10.1056/NEJM199204233261703 112.Novo Matos J, Payne JR, Seo J, Luis Fuentes V. Natural history of hypertrophic cardiomyopathy in cats from rehoming centers: The CatScan II study. Veterinary Internal Medicne. 2022;36(6):1900–12. DOI: 10.1111/jvim.16576 113.Marston S, Copeland O, Jacques A, Livesey K, Tsang V, McKenna WJ, et al. Evidence From Human Myectomy Samples That MYBPC3 Mutations Cause Hypertrophic Cardiomyopathy Through Haploinsufficiency. Circulation Research. 2009;105(3):219–22. DOI: 10.1161/CIRCRESAHA.109.202440 114.Marsiglia JDC, Credidio FL, De Oliveira TGM, Reis RF, Antunes MDO, De Araujo AQ, et al. Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. American Heart Journal. 2013;166(4):775–82. DOI: 10.1016/j.ahj.2013.07.029 115.Hathaway J, Heliö K, Saarinen I, Tallila J, Seppälä EH, Tuupanen S, et al. Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients. BMC Cardiovasc Disord. 2021;21(1):126. DOI: 10.1186/s12872-021-01927-5 116.Lopes LR, Zekavati A, Syrris P, Hubank M, Giambartolomei C, Dalageorgou C, et al. Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. J Med Genet. 2013;50(4):228–39. DOI: 10.1136/jmedgenet-2012-101270 117.Marziliano N, Merlini PA, Vignati G, Orsini F, Motta V, Bandiera L, et al. A Case of Compound Mutations in the MYBPC3 Gene Associated with Biventricular Hypertrophy and Neonatal Death. Neonatology. 2012;102(4):254–8. DOI: 10.1159/000339847 118.Zhou N, Qin S, Liu Y, Tang L, Zhao W, Pan C, et al. Whole-exome sequencing identifies rare compound heterozygous mutations in the MYBPC3 gene associated with severe familial hypertrophic cardiomyopathy. European Journal of Medical Genetics. 2018;61(8):434–41. DOI: 10.1016/j.ejmg.2018.03.001 119.Bick AG, Flannick J, Ito K, Cheng S, Vasan RS, Parfenov MG, et al. Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts. The American Journal of Human Genetics. 2012;91(3):513–9. DOI: 10.1016/j.ajhg.2012.07.017 120.Writing Committee Members, Ommen SR, Mital S, Burke MA, Day SM, Deswal A, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020;142(25). DOI: 10.1161/CIR.0000000000000938 121.Elliott PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. The Lancet. 2001;357(9254):420–4. DOI: 10.1016/S0140-6736(00)04005-8 122.O’Mahony C, Jichi F, Monserrat L, Ortiz-Genga M, Anastasakis A, Rapezzi C, et al. Inverted U-Shaped Relation Between the Risk of Sudden Cardiac Death and Maximal Left Ventricular Wall Thickness in Hypertrophic Cardiomyopathy. Circ: Arrhythmia and Electrophysiology. 2016;9(6):e003818. DOI: 10.1161/CIRCEP.115.003818 123.Santner V, Höller V, Ungericht M, Schwegel N, Zach D, Tichy H, et al. Left ventricular global longitudinal strain and diagnostic yield of genetic testing in hypertrophic cardiomyopathy in a multicenter registry analysis. Sci Rep. 2025;15(1):22573. DOI: 10.1038/s41598-025-05696-5 124.Grover S, Lloyd R, Perry R, Lou PW, Haan E, Yeates L, et al. Assessment of myocardial oxygenation, strain, and diastology in MYBPC3-related hypertrophic cardiomyopathy: a cardiovascular magnetic resonance and echocardiography study. European Heart Journal - Cardiovascular Imaging. 2019;20(8):932–8. DOI: 10.1093/ehjci/jey220 125.Santos EDS, Kuhn GDC, De Almeida AGC, Pimentel JVA, Figueiredo Neto NV, Tavares LRDS, et al. Genetic, Clinical, and Sociodemographic Profile of Individuals with Diagnosis or Family History of Hypertrophic Cardiomyopathy: Insights from a Prospective Cohort. Genes. 2025;16(9):1100. DOI: 10.3390/genes16091100 126.Rowin EJ, Hausvater A, Link MS, Abt P, Gionfriddo W, Wang W, et al. Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy. Circulation. 2017;136(25):2420–36. DOI: 10.1161/CIRCULATIONAHA.117.029267 127.Olivotto I, Maron BJ, Cecchi F. Clinical significance of atrial fibrillation in hypertrophic cardiomyopathy. Curr Cardiol Rep. 2001;3(2):141–6. DOI: 10.1007/s11886-001-0041-x 128.Roldán-Sevilla A, Palomino-Doza J, De Juan J, Sánchez V, Domínguez-González C, Salguero-Bodes R, et al. Missense Mutations in the FLNC Gene Causing Familial Restrictive Cardiomyopathy: Growing Evidence. Circ: Genomic and Precision Medicine. 2019;12(3). DOI: 10.1161/CIRCGEN.118.002388 129.Duboscq-Bidot L, Charron P, Ruppert V, Fauchier L, Richter A, Tavazzi L, et al. Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy. European Heart Journal. 2009;30(17):2128–36. DOI: 10.1093/eurheartj/ehp225 130.Crocini C, Arimura T, Reischmann S, Eder A, Braren I, Hansen A, et al. Impact of ANKRD1 mutations associated with hypertrophic cardiomyopathy on contraction parameters of engineered heart tissue. Basic Res Cardiol. 2013;108(3):349. DOI: 10.1007/s00395-013-0349-x 131.Lopes LR, Syrris P, Guttmann OP, O’Mahony C, Tang HC, Dalageorgou C, et al. Novel genotype–phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015;101(4):294–301. DOI: 10.1136/heartjnl-2014-306387pt_BR
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