Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-23T03:31:39.376Z Has data issue: false hasContentIssue false
  • English
  • Français

Familial hypertrophic cardiomyopathy caused by a de novo Gly716Arg mutation of the β-myosin heavy chain

Published online by Cambridge University Press:  10 May 2016

Peng Zhao ,
Hong-Li Cui ,
Ting-Ting He ,
Ji-Gang Wang ,
Dong Wang ,
Xin-Xing Feng ,
Yu-Bao Zou ,
Yi-Lu Wang ,
Ji-Zheng Wang  and
Ru-Tai Hui
...Show all authors
Peng Zhao
Affiliation:
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China
Hong-Li Cui
Affiliation:
Department of Forensic Medicine, Medical College of Qingdao University, Qingdao, China
Ting-Ting He
Affiliation:
Department of Forensic Medicine, Medical College of Qingdao University, Qingdao, China
Ji-Gang Wang*
Affiliation:
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China
Dong Wang
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xin-Xing Feng
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yu-Bao Zou
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yi-Lu Wang
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Ji-Zheng Wang
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Ru-Tai Hui
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Lei Song
Affiliation:
State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
*
Correspondence to: Dr J.-G. Wang, Department of Pathology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266003, China. Tel: +86 532 8291 9353; Fax: +86 532 8291 9900; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the β-myosin heavy chain. Neither the proband’s father nor the mother were carriers of this sequence variant; thus, the mutation was classified as “de novo”. Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.

Keywords

Hypertrophic cardiomyopathyGly716Argprognosis
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 3 , March 2017 , pp. 467 - 472
Check for updates
Copyright
© Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. 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. Coronary Artery Risk Development in (Young) Adults. Circulation 1995; 92: 785–789.CrossRefGoogle Scholar
2. Maron, BJ, Maron, MS. Hypertrophic cardiomyopathy. Lancet 2013; 381: 242–255.CrossRefGoogle ScholarPubMed
3. Zhao, P, Wang, JG, Gao, P, Li, X, Brewer, R. Sudden unexpected death from natural diseases: fifteen years’ experience with 484 cases in Seychelles. J Forensic Leg Med 2016; 37: 33–38.CrossRefGoogle ScholarPubMed
4. Maron, BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287: 1308–1320.CrossRefGoogle ScholarPubMed
5. 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 Am Coll Cardiol 2011; 58: e212–e260.CrossRefGoogle Scholar
6. Semsarian, C, Ingles, J, Maron, MS, Maron, BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol 2015; 65: 1249–1254.CrossRefGoogle ScholarPubMed
7. Maron, BJ, Maron, MS, Semsarian, C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol 2012; 60: 705–715.CrossRefGoogle ScholarPubMed
8. Gray, B, Ingles, J, Semsarian, C. Natural history of genotype positive-phenotype negative patients with hypertrophic cardiomyopathy. Int J Cardiol 2011; 152: 258–259.CrossRefGoogle ScholarPubMed
9. Anan, R, Greve, G, Thierfelder, L, et al. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest 1994; 93: 280–285.CrossRefGoogle ScholarPubMed
10. Hwang, TH, Lee, WH, Kimura, A, et al. Early expression of a malignant phenotype of familial hypertrophic cardiomyopathy associated with a Gly716Arg myosin heavy chain mutation in a Korean family. Am J Cardiol 1998; 82: 1509–1513.CrossRefGoogle Scholar
11. Ackerman, MJ, VanDriest, SL, Ommen, SR, et al. Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy: a comprehensive outpatient perspective. J Am Coll Cardiol 2002; 39: 2042–2048.CrossRefGoogle ScholarPubMed
12. Frisso, G, Limongelli, G, Pacileo, G, et al. A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy. Clin Genet 2009; 76: 91–101.CrossRefGoogle ScholarPubMed
13. Rai, TS, Ahmad, S, Bahl, A, 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: 189–196.CrossRefGoogle ScholarPubMed
14. Choi, JO, Yu, CW, Chun, NJ, et al. Long-term outcome of 4 Korean families with hypertrophic cardiomyopathy caused by 4 different mutations. Clin Cardiol 2010; 33: 430–438.CrossRefGoogle ScholarPubMed
15. Pytel, P, Husain, A, Moskowitz, I, et al. Ventricular fibrillation following autologous intramyocardial cell therapy for inherited cardiomyopathy. Cardiovasc Pathol 2010; 19: e33–e36.CrossRefGoogle ScholarPubMed
16. Garcia-Giustiniani, D, Arad, M, Ortiz-Genga, M, et al. Phenotype and prognostic correlations of the converter region mutations affecting the beta myosin heavy chain. Heart 2015; 101: 1047–1053.CrossRefGoogle ScholarPubMed
17. Geisterfer-Lowrance, AA, Kass, S, Tanigawa, G, et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 1990; 62: 999–1006.CrossRefGoogle ScholarPubMed
18. McNally, EM, Golbus, JR, Puckelwartz, MJ. Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 2013; 123: 19–26.CrossRefGoogle ScholarPubMed
19. Van Driest, SL, Jaeger, MA, Ommen, SR, et al. Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 44: 602–610.CrossRefGoogle ScholarPubMed
20. Richard, P, Charron, P, Carrier, L, et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003; 107: 2227–2232.CrossRefGoogle ScholarPubMed
21. Abchee, A, Marian, AJ. Prognostic significance of beta-myosin heavy chain mutations is reflective of their hypertrophic expressivity in patients with hypertrophic cardiomyopathy. J Investig Med 1997; 45: 191–196.Google ScholarPubMed
22. Huang, X, Song, L, Ma, AQ, et al. A malignant phenotype of hypertrophic cardiomyopathy caused by Arg719Gln cardiac beta-myosin heavy-chain mutation in a Chinese family. Clin Chim Acta 2001; 310: 131–139.CrossRefGoogle Scholar
23. McKenna, WJ. Hypertrophic cardiomyopathy: an update. Cardiologia 1993; 38: 277–281.Google ScholarPubMed
24. Miller, G, Colegrave, M, Peckham, M. N232S, G741R and D778G beta-cardiac myosin mutants, implicated in familial hypertrophic cardiomyopathy, do not disrupt myofibrillar organisation in cultured myotubes. FEBS Lett 2000; 486: 325–327.CrossRefGoogle Scholar