Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2019 Volume 20 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2019 Volume 20 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy

  • Authors:
    • Bo Wang
    • Jing Wang
    • Li‑Feng Wang
    • Fan Yang
    • Lei Xu
    • Wen‑Xia Li
    • Yang He
    • Lei Zuo
    • Qian‑Li Yang
    • Hong Shao
    • Dan Hu
    • Li‑Wen Liu
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of General Surgery, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China, Department of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5229-5238
    |
    Published online on: October 16, 2019
       https://doi.org/10.3892/mmr.2019.10754
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

β‑myosin heavy chain (MHC) 7 (MYH7) is the dominant pathogenic gene that harbors mutations in 20‑30% of cases of familial hypertrophic cardiomyopathy (HCM). The aim of this study was to elucidate the distribution and type of genetic variations among Chinese HCM families. From 2013 to 2017, the clinical data of 387 HCM probands and their families were collected. Targeted exome‑sequencing technology was used in all probands, and the selected mutations were subsequently verified by Sanger sequencing in the probands, family members and 300 healthy ethnic‑matched volunteers. Three‑dimensional models were created using Swiss‑PdbViewer 4.1, and further genetic analyses were performed to determine sequence conservation and frequency of the mutations. Among the 5 probands with double MYH7 mutations, 4 carried compound heterozygous mutations, and 1 carried monoallelic double mutations (A934V and E1387K). Four family members of the proband with monoallelic double mutations had the same mutation as the proband. Echocardiography and 12‑lead electrocardiography revealed abnormalities in the proband and 3 of the 4 carriers. The probands with compound heterozygous mutation had a higher left ventricular mass as revealed by echocardiography and higher QRS, SV1 and RV5+SV1 amplitudes than those with monoallelic double mutations (P<0.05). Simulation of the 3D structure of mutated proteins showed that the replacement of alanine by valine affected the flexibility of the MHC neck domain in case of the A934V mutation, whereas reactivity of the MHC rod domain was affected in the case of the E1387K mutation. In conclusion, we identified several novel HCM‑causing MYH7 mutations. More importantly, this is the first study to report a rare HCM family with monoallelic double mutations.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT and 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. 92:785–789. 1995. View Article : Google Scholar : PubMed/NCBI

2 

Maron BJ and Maron MS: Hypertrophic cardiomyopathy. Lancet. 381:242–255. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Semsarian C, Ingles J, Maron MS and Maron BJ: New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 65:1249–1254. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Maron BJ: Contemporary insights and strategies for risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Circulation. 121:445–456. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Maron BJ, Thompson PD, Ackerman MJ, Balady G, Berger S, Cohen D, Dimeff R, Douglas PS, Glover DW, Hutter AM Jr, et al: Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: A scientific statement from the American heart association council on nutrition, physical activity, and metabolism: Endorsed by the American college of cardiology foundation. Circulation. 115:1643–1655. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Ahmad F, Seidman JG and Seidman CE: The genetic basis for cardiac remodeling. Annu Rev Genomics Hum Genet. 6:185–216. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Waldmüller S, Sakthivel S, Saadi AV, Selignow C, Rakesh PG, Golubenko M, Joseph PK, Padmakumar R, Richard P, Schwartz K, et al: Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 35:623–636. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, 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. Circulation. 124:2761–2796. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Authors/Task Force members, ; Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, 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). Eur Heart J. 35:2733–2779. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Maron BJ, Maron MS and 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. 9:57–63. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Wang J, Wang Y, Zou Y, Sun K, Wang Z, Ding H, Yuan J, Wei W, Hou Q, Wang H, et al: Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy. Eur J Heart Fail. 16:950–957. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Zou Y, Wang J, Liu X, Wang Y, Chen Y, Sun K, Gao S, Zhang C, Wang Z, Zhang Y, et al: Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy. Mol Biol Rep. 40:3969–3976. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Helms AS, Alvarado FJ, Yob J, Tang VT, Pagani F, Russell MW, Valdivia HH and Day SM: Genotype-dependent and -independent calcium signaling dysregulation in human hypertrophic cardiomyopathy. Circulation. 134:1738–1748. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Cam FS and Güray M: Hypertrophic cardiomyopathy: Pathological features and molecular pathogenesis. Anadolu Kardiyol Derg. 4:327–330. 2004.PubMed/NCBI

15 

Wang L, Zuo L, Hu J, Shao H, Lei C, Qi W, Liu Y, Miao Y, Ma X, Huang CL, et al: Dual LQT1 and HCM phenotypes associated with tetrad heterozygous mutations in KCNQ1, MYH7, MYLK2, and TMEM70 genes in a three-generation Chinese family. Europace. 18:602–609. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Guex N and Peitsch MC: SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis. 18:2714–2723. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, 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. 17:405–424. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Lopes LR, Zekavati A, Syrris P, Hubank M, Giambartolomei C, Dalageorgou C, Jenkins S, McKenna W, Uk10k Consortium, Plagnol V and Elliott PM: Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. J Med Genet. 50:228–239. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Wang S, Zou Y, Fu C, Xu X, Wang J, Song L, Wang H, Chen J, Wang J, Huan T and Hui R: Worse prognosis with gene mutations of beta-myosin heavy chain than myosin-binding protein C in Chinese patients with hypertrophic cardiomyopathy. Clin Cardiol. 31:114–118. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Woo A, Rakowski H, Liew JC, Zhao MS, Liew CC, Parker TG, Zeller M, Wigle ED and Sole MJ: Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: Critical functional sites determine prognosis. Heart. 89:1179–1185. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Walsh R, Rutland C, Thomas R and Loughna S: Cardiomyopathy: A systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations. Cardiology. 115:49–60. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Kelly MA, Caleshu C, Morales A, Buchan J, Wolf Z, Harrison SM, Cook S, Dillon MW, Garcia J, Haverfield E, et al: Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: Recommendations by ClinGen's inherited cardiomyopathy expert panel. Genet Med. 20:351–359. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Viswanathan SK, Sanders HK, McNamara JW, Jagadeesan A, Jahangir A, Tajik AJ and Sadayappan S: Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage. PLoS One. 12:e01879482017. View Article : Google Scholar : PubMed/NCBI

24 

Guidelines for the diagnosis and treatment for Chinese adult patients with hypertrophic cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi. 45:1015–1032. 2017.(In Chinese). PubMed/NCBI

25 

Elliott PM, Gimeno JR, Tomé MT, Shah J, Ward D, Thaman R, Mogensen J and McKenna WJ: Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J. 27:1933–1941. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F and Maron BJ: Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med. 348:295–303. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang B, Wang J, Wang LF, Yang F, Xu L, Li WX, He Y, Zuo L, Yang QL, Shao H, Shao H, et al: Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy. Mol Med Rep 20: 5229-5238, 2019.
APA
Wang, B., Wang, J., Wang, L., Yang, F., Xu, L., Li, W. ... Liu, L. (2019). Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy. Molecular Medicine Reports, 20, 5229-5238. https://doi.org/10.3892/mmr.2019.10754
MLA
Wang, B., Wang, J., Wang, L., Yang, F., Xu, L., Li, W., He, Y., Zuo, L., Yang, Q., Shao, H., Hu, D., Liu, L."Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy". Molecular Medicine Reports 20.6 (2019): 5229-5238.
Chicago
Wang, B., Wang, J., Wang, L., Yang, F., Xu, L., Li, W., He, Y., Zuo, L., Yang, Q., Shao, H., Hu, D., Liu, L."Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy". Molecular Medicine Reports 20, no. 6 (2019): 5229-5238. https://doi.org/10.3892/mmr.2019.10754
Copy and paste a formatted citation
x
Spandidos Publications style
Wang B, Wang J, Wang LF, Yang F, Xu L, Li WX, He Y, Zuo L, Yang QL, Shao H, Shao H, et al: Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy. Mol Med Rep 20: 5229-5238, 2019.
APA
Wang, B., Wang, J., Wang, L., Yang, F., Xu, L., Li, W. ... Liu, L. (2019). Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy. Molecular Medicine Reports, 20, 5229-5238. https://doi.org/10.3892/mmr.2019.10754
MLA
Wang, B., Wang, J., Wang, L., Yang, F., Xu, L., Li, W., He, Y., Zuo, L., Yang, Q., Shao, H., Hu, D., Liu, L."Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy". Molecular Medicine Reports 20.6 (2019): 5229-5238.
Chicago
Wang, B., Wang, J., Wang, L., Yang, F., Xu, L., Li, W., He, Y., Zuo, L., Yang, Q., Shao, H., Hu, D., Liu, L."Genetic analysis of monoallelic double MYH7 mutations responsible for familial hypertrophic cardiomyopathy". Molecular Medicine Reports 20, no. 6 (2019): 5229-5238. https://doi.org/10.3892/mmr.2019.10754
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team