A novel Loss-of-function Mutation in MYBPC3 Causes familial hypertrophic cardiomyopathy with extreme intrafamilial phenotypic heterogeneity

1Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: Echocardiographic analysis of 4111 subjects in the CARDIA study. Circulation. 1995; 92(4): 785-789. Maron BJ Gardin JM Flack JM Gidding SS Kurosaki TT Bild DE Prevalence of hypertrophic cardiomyopathy in a general population of young adults: Echocardiographic analysis of 4111 subjects in the CARDIA study Circulation 1995 924 785 78910.1161/01.CIR.92.4.785Search in Google Scholar

2Zou Y, Song L, Wang Z, Ma A, Liu T, Gu H, et al. Prevalence of idiopathic hypertrophic cardiomyopathy in China: A population-based echocardiographic analysis of 8080 adults. Am J Med. 2004; 116(1): 14-18. Zou Y Song L Wang Z Ma A Liu T Gu H et al Prevalence of idiopathic hypertrophic cardiomyopathy in China: A population-based echocardiographic analysis of 8080 adults Am J Med 2004 1161 14 1810.1016/j.amjmed.2003.05.009Search in Google Scholar

3Maron BJ, Bonow RO, Cannon RO 3rd, Leon MB, Epstein SE. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (2). N Engl J Med. 1987; 316(14): 844-852. Maron BJ Bonow RO Cannon RO 3rd Leon MB Epstein SE Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (2) N Engl J Med 1987 31614 844 85210.1056/NEJM198704023161405Search in Google Scholar

4Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation. 1995; 92(7): 1680-1692. Wigle ED Rakowski H Kimball BP Williams WG Hypertrophic cardiomyopathy. Clinical spectrum and treatment Circulation 1995 927 1680 169210.1161/01.CIR.92.7.1680Search in Google Scholar

5Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of hypertrophic cardiomyopathy. N Engl J Med. 1997; 336(11): 775-785. Spirito P Seidman CE McKenna WJ Maron BJ The management of hypertrophic cardiomyopathy N Engl J Med 1997 33611 775 78510.1056/NEJM199703133361107Search in Google Scholar

6Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003; 107(17): 2227-2232. Richard P Charron P Carrier L Ledeuil C Cheav T Pichereau C et al Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy Circulation 2003 10717 2227 223210.1161/01.CIR.0000066323.15244.54Search in Google Scholar

7Merante F, Myint T, Tein I, Benson L, Robinson BH. An additional mitochondrial tRNA (Ile) point mutation (A-to-G at nucleotide 4295) causing hypertrophic cardiomyopathy. Hum Mutat. 1996; 8(3): 216-222. Merante F Myint T Tein I Benson L Robinson BH An additional mitochondrial tRNA (Ile) point mutation (A-to-G at nucleotide 4295) causing hypertrophic cardiomyopathy Hum Mutat 1996 83 216 22210.1002/(SICI)1098-1004(1996)8:3<216::AID-HUMU4>3.0.CO;2-7Search in Google Scholar

8Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, et al. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 2002; 109(3): 357-362. Arad M Benson DW Perez-Atayde AR McKenna WJ Sparks EA Kanter RJ et al Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy J Clin Invest 2002 1093 357 36210.1172/JCI0214571Search in Google Scholar

9Seidman JG, Seidman C. Transcription factor haploinsufficiency: when half a loaf is not enough. J Clin Invest 2002; 109(4): 451-455. Seidman JG Seidman C Transcription factor haploinsufficiency: when half a loaf is not enough J Clin Invest 2002 1094 451 45510.1172/JCI0215043Search in Google Scholar

10Charron P, Dubourg O, Desnos M, Bennaceur M, Carrier L, Camproux AC, et al. Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene. Circulation 1998; 97(22): 2230-2236. Charron P Dubourg O Desnos M Bennaceur M Carrier L Camproux AC et al Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene Circulation 1998 9722 2230 223610.1161/01.CIR.97.22.2230Search in Google Scholar

11Charron P, Dubourg O, Desnos M, Isnard R, Hagege A, Bonne G, et al. Genotype-phenotype correlations in familial hypertrophic cardiomyopathy. A comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes. Eur Heart J. 1998; 19(1): 139-145. Charron P Dubourg O Desnos M Isnard R Hagege A Bonne G et al Genotype-phenotype correlations in familial hypertrophic cardiomyopathy. A comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes Eur Heart J 1998 191 139 14510.1053/euhj.1997.05759503187Search in Google Scholar

12Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, 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. Niimura H Bachinski LL Sangwatanaroj S Watkins H Chudley AE 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 33818 1248 125710.1056/NEJM1998043033818029562578Search in Google Scholar

13Biagini E, Olivotto I, Iascone M, Parodi MI, Girolami F, Frisso G, et al. Significance of sarcomere gene mutations analysis in the end-stage phase of hypertrophic cardiomyopathy. Am J Cardiol. 2014; 114(5): 769-776. Biagini E Olivotto I Iascone M Parodi MI Girolami F Frisso G et al Significance of sarcomere gene mutations analysis in the end-stage phase of hypertrophic cardiomyopathy Am J Cardiol 2014 1145 769 77610.1016/j.amjcard.2014.05.06525037680Search in Google Scholar

14Rodríguez-García MI, Monserrat L, Ortiz M, Fernández X, Cazón L, Núñez L, et al. Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy. BMC Med Genet. 2010; 11: 67. Rodríguez-García MI Monserrat L Ortiz M Fernández X Cazón L Núñez L et al Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy BMC Med Genet 2010 11 6710.1186/1471-2350-11-67288097420433692Search in Google Scholar

15Marsiglia JD, Credidio FL, de Oliveira TG, Reis RF, Antunes Mde O, de Araujo AQ, et al. Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. Am Heart J. 2013; 166(4): 775-782. Marsiglia JD Credidio FL de Oliveira TG Reis RF Antunes Mde O de Araujo AQ et al Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy Am Heart J 2013 1664 775 78210.1016/j.ahj.2013.07.02924093860Search in Google Scholar

16Liu X, Jiang T, Piao C, Li X, Guo J, Zheng S, et al. Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing. Sci Rep. 2015; 5: 11411. Liu X Jiang T Piao C Li X Guo J Zheng S et al Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing Sci Rep 2015 5 1141110.1038/srep11411447369026090888Search in Google Scholar

17Emrahi L, Tabrizi MT, Gharehsouran J, et al. Spectrum of MYBPC3 Gene Mutations in Patients with Hypertrophic Cardiomyopathy, Reporting Two Novel Mutations from North-West of Iran. Clin Lab. 2016; 62(5): 757-764. Emrahi L Tabrizi MT Gharehsouran J et al Spectrum of MYBPC3 Gene Mutations in Patients with Hypertrophic Cardiomyopathy, Reporting Two Novel Mutations from North-West of Iran Clin Lab 2016 625 757 76410.7754/Clin.Lab.2014.14113427348999Search in Google Scholar

18Maron BJ, Maron MS, Semsarian C. Double or compound sarcomere mutations in hypertrophic cardiomyopathy: a potential link to sudden death in the absence of conventional risk factors. Heart Rhythm. 2012; 9(1): 57-63. Maron BJ Maron MS Semsarian C Double or compound sarcomere mutations in hypertrophic cardiomyopathy: a potential link to sudden death in the absence of conventional risk factors Heart Rhythm 2012 91 57 6310.1016/j.hrthm.2011.08.00921839045Search in Google Scholar

19Marziliano 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): 254-258. 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 1024 254 25810.1159/00033984722907696Search in Google Scholar

20Schaefer E, Helms P, Marcellin L, Desprez P, Billaud P, Chanavat V, et al. Next-generation sequencing (NGS) as a fast molecular diagnosis tool for left ventricular noncompaction in an infant with compound mutations in the MYBPC3 gene. Eur J Med Genet. 2014; 57(4): 129-132. Schaefer E Helms P Marcellin L Desprez P Billaud P Chanavat V et al Next-generation sequencing (NGS) as a fast molecular diagnosis tool for left ventricular noncompaction in an infant with compound mutations in the MYBPC3 gene Eur J Med Genet 2014 574 129 13210.1016/j.ejmg.2014.02.01524602869Search in Google Scholar

21Wessels 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): 922-928. 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 237 922 92810.1038/ejhg.2014.211446349925335496Search in Google Scholar

22Driest SLV, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, et al. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2004; 44(9): 1903-1310. Driest SLV Vasile VC Ommen SR Will ML Tajik AJ Gersh BJ et al Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy J Am Coll Cardiol 2004 449 1903 131010.1016/j.jacc.2004.07.04515519027Search in Google Scholar

23Erdmann 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. 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 644 339 34910.1034/j.1399-0004.2003.00151.x12974739Search in Google Scholar

24Zhang R, Chen S, Han P, Chen F, Kuang S, Meng Z, et al. Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome. J Cell Mol Med. 2020; 24(2): 1906-1916. Zhang R Chen S Han P Chen F Kuang S Meng Z et al Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome J Cell Mol Med 2020 242 1906 191610.1111/jcmm.14887699168231840411Search in Google Scholar

25Richards 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. Genet Med. 2015; 17(5): 405-424. 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 Genet Med 2015 175 405 42410.1038/gim.2015.30454475325741868Search in Google Scholar

26Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014; 11(4): 361-362. Schwarz JM Cooper DN Schuelke M Seelow D MutationTaster2: mutation prediction for the deep-sequencing age Nat Methods 2014 114 361 36210.1038/nmeth.289024681721Search in Google Scholar

27Marian AJ. On genetic and phenotypic variability of hypertrophic cardiomyopathy: nature versus nurture. J Am Coll Cardiol. 2001; 38(2): 331-334. Marian AJ On genetic and phenotypic variability of hypertrophic cardiomyopathy: nature versus nurture J Am Coll Cardiol 2001 382 331 33410.1016/S0735-1097(01)01389-4Search in Google Scholar

28Watkins H, Conner D, Thierfelder L, Jarcho JA, Mac-Rae C, McKenna WJ, et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet. 1995; 11(4): 434-437. Watkins H Conner D Thierfelder L Jarcho JA Mac-Rae C McKenna WJ et al Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy Nat Genet 1995 114 434 43710.1038/ng1295-4347493025Search in Google Scholar

29Gómez J, Reguero JR, Morís C, Martín M, Alvarez V, Alonso B, et al. Mutation analysis of the main hypertrophic cardiomyopathy genes using multiplex amplification and semiconductor next-generation sequencing. Circ J. 2014; 78(12): 2963-2971. Gómez J Reguero JR Morís C Martín M Alvarez V Alonso B et al Mutation analysis of the main hypertrophic cardiomyopathy genes using multiplex amplification and semiconductor next-generation sequencing Circ J 2014 7812 2963 297110.1253/circj.CJ-14-062825342278Search in Google Scholar

30Loar RW, Bos JM, Will ML, Ommen SR, Ackerman MJ. Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults. Congenital Heart Disease. 2015; 10(6): 529-536. Loar RW Bos JM Will ML Ommen SR Ackerman MJ Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults Congenital Heart Disease 2015 106 529 53610.1111/chd.1228026061417Search in Google Scholar

31Maron BJ. Hypertrophic cardiomyopathy: an important global disease. Am J Med. 2004; 116(1): 63-65. Maron BJ Hypertrophic cardiomyopathy: an important global disease Am J Med 2004 1161 63 6510.1016/j.amjmed.2003.10.01214706671Search in Google Scholar

32Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287(10): 1308-1320. Maron BJ Hypertrophic cardiomyopathy: a systematic review JAMA 2002 28710 1308 132010.1001/jama.287.10.130811886323Search in Google Scholar

33Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011; 58(25): 2703-2738. Gersh BJ Maron BJ Bonow RO Dearani JA Fifer MA Link MS et al 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2011; 5825 2703 273810.1016/j.jacc.2011.10.82522075468Search in Google Scholar

34Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res. 2017; 121(7): 749-770. Marian AJ Braunwald E Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy Circ Res 2017 1217 749 77010.1161/CIRCRESAHA.117.311059565455728912181Search in Google Scholar

35Wijnker PJM, Friedrich FW, Dutsch A, Reischmann S, Eder A, Mannhardt I, et al. Comparison of the effects of a truncating and a missense MYBPC3 mutation on contractile parameters of engineered heart tissue. J Mol Cell Cardiol. 2016; 97: 82-92. Wijnker PJM Friedrich FW Dutsch A Reischmann S Eder A Mannhardt I et al Comparison of the effects of a truncating and a missense MYBPC3 mutation on contractile parameters of engineered heart tissue J Mol Cell Cardiol 2016 97 82 9210.1016/j.yjmcc.2016.03.00327108529Search in Google Scholar

36Helms AS, Davis FM, Coleman D, Bartolone SN, Glazier AA, Pagani F, et al. Sarcomere mutation specific expression patterns in human hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2014; 7(4): 434-443. Helms AS Davis FM Coleman D Bartolone SN Glazier AA Pagani F et al Sarcomere mutation specific expression patterns in human hypertrophic cardiomyopathy Circ Cardiovasc Genet 2014 74 434 44310.1161/CIRCGENETICS.113.000448425465625031304Search in Google Scholar

37Mohamed IA, Krishnamoorthy NT, Nasrallah GK, Da’as SI. The role of cardiac myosin binding protein C3 in hypertrophic cardiomyopathy progress and novel therapeutic opportunities. J Cell Physiol 2017; 232(7): 1650-1659. Mohamed IA Krishnamoorthy NT Nasrallah GK Da’as SI The role of cardiac myosin binding protein C3 in hypertrophic cardiomyopathy progress and novel therapeutic opportunities J Cell Physiol 2017 2327 1650 165910.1002/jcp.2563927731493Search in Google Scholar

38Dai Y, Liang S, Dong X, Zhao Y, Ren H, Guan Y, et al. Whole exome sequencing identified a novel DAG1 mutation in a patient with rare, mild and late age of onset muscular dystrophy-dystroglycanopathy. J Cell Mol Med. 2019; 23(2): 811-818. Dai Y Liang S Dong X Zhao Y Ren H Guan Y et al Whole exome sequencing identified a novel DAG1 mutation in a patient with rare, mild and late age of onset muscular dystrophy-dystroglycanopathy J Cell Mol Med 2019 232 811 81810.1111/jcmm.13979634915130450679Search in Google Scholar

39Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010; 42(1): 30-35. Ng SB Buckingham KJ Lee C Bigham AW Tabor HK Dent KM et al Exome sequencing identifies the cause of a mendelian disorder Nat Genet 2010 421 30 3510.1038/ng.499284788919915526Search in Google Scholar