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A novel MYBPC3 c.2737+1 (IVS26) G>T mutation responsible for high-risk hypertrophic cardiomyopathy

Published online by Cambridge University Press:  21 November 2019

Wuyang Tong Open the ORCID record for Wuyang Tong [Opens in a new window] ,
Wei Liu ,
Hong Guo ,
Jiang Wang ,
Shiyong Yu ,
Jihang Zhang ,
Chuan Liu ,
Jia Chen  and
Xiaohui Zhao
Wuyang Tong
Affiliation:
Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
Wei Liu
Affiliation:
Institute of Immunology, Army Medical University, Chongqing, China
Hong Guo
Affiliation:
Department of Medical Genetics, College of Basic Medical Science, Army Medical University, Chongqing, China
Jiang Wang
Affiliation:
Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
Shiyong Yu
Affiliation:
Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
Jihang Zhang
Affiliation:
Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
Chuan Liu
Affiliation:
Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
Jia Chen
Affiliation:
Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, China
Xiaohui Zhao*
Affiliation:
Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
*
Author for correspondence: X. Zhao, MD, Institute of Cardiovascular Research, Xinqiao Hospital, Army Medical University, 183 Xinqiao Road, Shapingba District, Chongqing 400037, China. Tel: +8613508332848. E-mail: [email protected]
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Abstract

Background:

Hypertrophic cardiomyopathy is an autosomal dominant hereditary disease characterised by left ventricular asymmetry hypertrophy. However, our knowledge of the genetic background in hypertrophic cardiomyopathy cases is limited. Here, we aimed to evaluate pathogenic gene mutations in a family with high-risk hypertrophic cardiomyopathy and analyse the genotype/phenotype relationships in this family.

Methods:

The proband, her parents, and her niece underwent whole-exome sequencing, and the genotypes of family members were identified using Sanger sequencing. mRNA expression was detected using reverse transcription sequencing. Structural impairments were predicted by homologous modelling. A family survey was conducted for patients with positive results to obtain information on general clinical symptoms, electrocardiography, ambulatory electrocardiography, echocardiography, and 3.0T cardiac magnetic resonance findings. Regular follow-up was performed for up to 6 months.

Results:

Five family members, including the proband, carried a cleavage site mutation in the MYBPC3 gene (c.2737+1 (IVS26) G>T), causing exon 26 of the MYBPC3 gene transcript to be skipped and leading to truncation of cardiac myosin-binding protein C. Family survey showed that the earliest onset age was 13 years old, and three people had died suddenly at less than 40 years old. Three pathogenic gene carriers were diagnosed with hypertrophic cardiomyopathy, and all showed severe ventricular septal hypertrophy.

Conclusion:

The c.2737+1 (IVS26) G>T mutation in the MYBPC3 gene led to exon 26 skipping, thereby affecting the structure and function of cardiac myosin-binding protein C and leading to severe ventricular hypertrophy and sudden death.

Keywords

Hypertrophic cardiomyopathyMYBPC3 genegenotypephenotype
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 1 , January 2020 , pp. 100 - 106
Copyright
© Cambridge University Press 2019

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