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Novel pathogenic variant of MYBPC3 responsible for hypertrophic cardiomyopathy

Published online by Cambridge University Press:  28 June 2021

Xiaofei Yang Open the ORCID record for Xiaofei Yang [Opens in a new window] ,
Zhenghao Li ,
Qingfa Wang ,
Yongfa Zhang  and
Cuifen Zhao
Xiaofei Yang
Affiliation:
Department of Pediatrics, Yidu Central Hospital of Weifang, Weifang, Shandong, China Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong, China
Zhenghao Li
Affiliation:
Department of Pediatrics, Yidu Central Hospital of Weifang, Weifang, Shandong, China
Qingfa Wang
Affiliation:
Department of Pediatrics, Yidu Central Hospital of Weifang, Weifang, Shandong, China
Yongfa Zhang
Affiliation:
Department of Pediatrics, Yidu Central Hospital of Weifang, Weifang, Shandong, China
Cuifen Zhao*
Affiliation:
Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, Shandong, China
*
Author for correspondence: Dr C. Zhao, MD, PhD, Department of Pediatrics, Qilu Hospital, Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China. Tel: +86 531 82169940; Fax: +86 531 86927544. E-mail: zhaocuifen@sdu.edu.cn.
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Abstract

Objectives:

This study aims to investigate the pathogenic gene variant in a family with hypertrophic cardiomyopathy by using whole-exome sequencing and to explore the relationship between the gene variant and clinical phenotype.

Methods:

Peripheral blood was collected from a family with hypertrophic cardiomyopathy, and deoxyribonucleic acid was extracted. The possible pathogenic genes were detected by whole-exome sequencing, and the variant was verified by Sanger sequencing. Functional change in the variant was predicted by bioinformatics software. Clinical data of the family members are analysed simultaneously.

Results:

The proband carries a novel heterozygous nonsense variant of MYBPC3:c.2731G > T (p.E911X). The analysis of amino acid conservation suggests that the variation is highly conserved. The three-dimensional protein structure shows that the variant in MYBPC3 results in the incompleteness of the fibronectintype-III2 (p872–967) domain and deletion of Ig-like C2-type 6 (p971–1065) and fibronectin type-III 3 and Ig-like C2-type 7 (p1181–1274) domains, in which p1253–1268 is predicted to have a transmembrane helix structure. Clinical data indicate that the phenotypes of variant carriers with hypertrophic cardiomyopathy are diverse, suggesting the functional damages to the protein of MYBPC3.

Conclusion:

The phenotypes of variant carriers with hypertrophic cardiomyopathy caused by the novel variant in MYBPC3: c.2731G > T (p.E911X) exhibit variable severity and clinical manifestations. Whole-exome sequencing can be used to comprehensive screen hypertrophic cardiomyopathy genes and provide a strong basis for early screening and accurate diagnosis and treatment of hypertrophic cardiomyopathy in children.

Keywords

Hypertrophic cardiomyopathyMYBPC3whole-exome sequencingvariantphenotype
Type
Original Article
Information
Cardiology in the Young , Volume 32 , Issue 4 , April 2022 , pp. 539 - 544
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

Xiaofei Yang and Zhenghao Li contributed equally to this work and should be considered co-first authors.

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