Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (9): 83-87.doi: 10.6040/j.issn.1671-7554.0.2019.579

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Relationship between cardiac myosin-binding protein p.L808M and c.2417_2419delACA gene mutation and familial hypertrophic cardiomyopathy

LIU Xiaoman1, LI Hong1, YANG Guang1, JIN Cuixiang2   

  1. 1. Department of Cardiology, Shandong Province Qianfoshan Hospital, Jinan 250014, Shandong, China;
    2. Department of Cardiology, School Hospital of Shandong University, Jinan 250002, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To explore the disease-causing gene mutation of hypertrophic cardiomyopathy(HCM), and to analyze the correlation between the genotype and phenotype. Methods The exons in 26 HCM-related genes were amplified by target exon trapping sequencing and tested in one HCM proband to identify the pathogenic mutations. The identified mutations were detected with Sanger sequencing in all family members of the proband and 100 healthy volunteers. The clinical manifestations, physical examinations, electrocardiography and echocardiography were analyzed, and the relationship between genotype and phenotype was analyzed. Results Two mutations(p.L808M and c.2417_2419delACA)in the 26th exon of the MYBPC3 gene were identified in a 73-year-old female patient, but no such mutation was detected in the 100 healthy volunteers. The patient began to have symptoms of chest distress and palpitation since the age of 57. Totally 5 family members carried the mutant gene, including 2 HCM patients and 3 asymptomatic 山 东 大 学 学 报 (医 学 版)57卷9期 -刘晓曼,等.心脏型肌球蛋白结合蛋白C p.L808M和c.2417_2419delACA基因突变与家族性肥厚型心肌病的关系 \=-carriers. No history of sudden cardiac death was observed. Conclusion Functional analysis of the sequences suggested that the double mutations may cause significant alteration of the protein function. MYBPC3 p.L808M and c.2417_2419delACA mutations may be the pathogenic mutations of this HCM family.

Key words: Cardiomyopathy, Hypertrophic, Cardiac myosin binding protein-C, Mutation

CLC Number: 

  • R542.2
[1] 中国医师协会心力衰竭专业委员会, 中华心力衰竭和心肌病杂志编辑委员会. 中国肥厚型心肌病管理指南2017[J].中华心力衰竭和心肌病杂志(中英文), 2017(2):65-86.
[2] Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence of hypertrophic cardiomyopathy[J]. J Am Coll Cardiol, 2015, 65(12):1249-1254.
[3] Ehlermann P, Weichenhan D, Zehelein J, et al. Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene[J]. BMC Med Genet, 2008, 9:95. doi:10.1186/1471-2350-9-95.
[4] Sabater-Molina M, Pérez-Sánchez I, Hernández Del Rincón JP, et al. Genetics of hypertrophic cardiomyopathy: A review of current state[J]. Clin Genet, 2018, 93(1):3-14.
[5] Jarcho JA, McKenna W, Pare JA, et al. Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1[J]. N Engl J Med, 1989, 321(20):1372-1378.
[6] Viswanathan SK, Sanders HK, McNamara JW, et al. Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage[J]. PLoS One, 2017, 12(11):e0187948. doi:10.1371/journal.pone.0187948.ecollection 2017.
[7] Behrens-Gawlik V, Mearini G, Gedicke-Hornung C, et al. MYBPC3 in hypertrophic cardiomyopathy: from mutation identification to RNA-based correction[J]. Pflugers Arch, 2014, 466(2):215-223.
[8] Kuster DW, Sadayappan S. MYBPC3s alternate ending: consequences and therapeutic implications of a highly prevalent 25 bp deletion mutation[J]. Pflugers Arch, 2014, 466(2):207-213.
[9] Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons[J]. J Am Coll Cardiol, 2011, 58(25):212-260.
[10] Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology(ESC)[J]. Eur Heart J, 2014, 35(39):2733-2779.
[11] Morimoto S. Sarcomeric proteins and inherited cardiomyopathies[J]. Cardiovasc Res, 2008, 77(4):659-666.
[12] Prondzynski M, Krämer E, Laufer SD, et al. Evaluation of MYBPC3 trans-Splicing and gene replacement as therapeutic options in human iPSC-Derived cardiomyocytes[J]. Mol Ther Nucleic Acids, 2017, 7:475-486. doi:10.1016/j.omtn.2017.05.008.
[13] García-Giustiniani D, Arad M, Ortíz-Genga M, et al. Phenotype and prognostic correlations of the converter region mutations affecting the β myosin heavy chain[J].Heart, 2015, 101(13):1047-1053.
[14] Marques MA, de Oliveira GA. Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the hypertrophic cardiomyopathy phenotype[J]. Front Physiol, 2016, 7:429.
[15] 李静, 刘丽文, 纳丽莎, 等. 心脏肌球蛋白结合蛋白C基因P1208fs突变与家族性肥厚型心肌病的关系[J].中华心血管病杂志, 2016, 44(4):321-326. LI Jing, LIU Liwen, NA Lisha, et al. P1208fs mutation in the cardiac myosin binding protein C is associated with hypertrophic cardiomyopathy in a Chinese pedigree[J]. Chin J Cardiol, 2016, 44(4):321-326.
[16] Page SP, Kounas S, Syrris P, et al. Cardiac myosin binding protein-C mutations in families with hypertrophic cardiomyopathy: disease expression in relation to age, gender, and long term outcome[J]. Circ Cardiovasc Genet, 2012, 5(2):156-166.
[17] Rubattu S, Bozzao C, Pennacchini E, et al. A next-generation sequencing approach to identify gene mutations in early- and late-onset hypertrophic cardiomyopathy patients of an italian cohort[J]. Int J Mol Sci, 2016, 17(8):1239.
[18] McTaggart DR, Ogden KJ, Marathe JA. A long term follow-up study of carriers of hypertrophic cardiomyopathy mutations[J]. Heart Lung Circ, 2017, 26(1):18-24.
[19] Ko C, Arscott P, Concannon M, et al. Genetic testing impacts the utility of prospective familial screening in hypertrophic cardiomyopathy through identification of a nonfamilial subgroup[J]. Genet Med, 2018, 20(1):69-75.
[20] Ben Jehuda R, Eisen B, Shemer Y, et al. CRISPR correction of the PRKAG2 gene mutation in the patient's induced pluripotent stem cell-derived cardiomyocytes eliminates electrophysiological and structural abnormalities[J]. Heart Rhythm, 2018, 15(2):267-276.
[21] Ma H, Marti-Gutierrez N, Park SW, et al. Correction of a pathogenic gene mutation in human embryos[J]. Nature, 2017, 548(7668):413-419.
[22] Hammond SM, Wood MJ. Genetic therapies for RNA mis-splicing diseases[J]. Trends Genet, 2011, 27(5):196-205.
[23] Bongianino R, Denegri M, Mazzanti A, et al. Allele-Specific silencing of mutant mRNA rescues ultrastructural and arrhythmic phenotype in mice carriers of the R4496C mutation in the ryanodine receptor gene(RYR2)[J]. Circ Res, 2017, 121(5):525-536.
[24] Mearini G, Stimpel D, Krämer E, et al. Repair of Mybpc3 mRNA by 5-trans-splicing in a Mouse Model of Hypertrophic Cardiomyopathy[J]. Mol Ther Nucleic Acids, 2013, 2:102. doi:10.1038/mtna.2013.31.
[25] Mearini G, Stimpel D, Geertz B, et al. Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice[J]. Nat Commun, 2014, 5:5515.doi:10.1038/wcomms 6515.
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