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Novel pathogenic variant of MYBPC3 responsible for hypertrophic cardiomyopathy
Published online by Cambridge University Press: 28 June 2021
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.
Information
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- Original Article
- Information
- Copyright
- © The Author(s), 2021. Published by Cambridge University Press
Footnotes
Xiaofei Yang and Zhenghao Li contributed equally to this work and should be considered co-first authors.
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