<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Cardiomyopathies are a heterogeneous group of diseases predominantly affecting the heart muscle and often lead to progressive heart failure-related disability or cardiovascular death. Hypertrophic cardiomyopathy (HCM) is a cardiac muscle disorder mostly caused by the mutations in genes encoding cardiac sarcomere. Germ-line mutations in <italic>MYBPC3</italic> causes hypertrophic cardiomyopathy (HCM). However, most of the HCM associated <italic>MYBPC3</italic> mutations were truncating mutations. Extreme phenotypic heterogeneity was observed among HCM patients with <italic>MYBPC3</italic> mutations. In this study, we investigated a Chinese man who presented with HCM. Whole exome sequencing identified a novel heterozygous deletion (c.3781_3785delGAGGC) in exon 33 of the <italic>MYBPC3</italic> in the proband. This heterozygous variant causes frameshift (p.Glu1261Thrfs*3), which predicted to form a truncated MYBPC3 protein. The proband’s father also carries this variant in a heterozygous state while the proband’s mother did not harbor this variant. Here, we report on a novel deletion in the <italic>MYBPC3</italic> gene associated with HCM. We also highlight the importance of whole exome sequencing for molecular diagnosis for the patients with familial HCM.</p></abstract>

Cardiomyopathies are a heterogeneous group of diseases predominantly affecting the heart muscle and often lead to progressive heart failure-related disability or cardiovascular death. Hypertrophic cardiomyopathy (HCM) is a cardiac muscle disorder mostly caused by the mutations in genes encoding cardiac sarcomere. Germ-line mutations in MYBPC3 causes hypertrophic cardiomyopathy (HCM). However, most of the HCM associated MYBPC3 mutations were truncating mutations. Extreme phenotypic heterogeneity was observed among HCM patients with MYBPC3 mutations. In this study, we investigated a Chinese man who presented with HCM. Whole exome sequencing identified a novel heterozygous deletion (c.3781_3785delGAGGC) in exon 33 of the MYBPC3 in the proband. This heterozygous variant causes frameshift (p.Glu1261Thrfs*3), which predicted to form a truncated MYBPC3 protein. The proband’s father also carries this variant in a heterozygous state while the proband’s mother did not harbor this variant. Here, we report on a novel deletion in the MYBPC3 gene associated with HCM. We also highlight the importance of whole exome sequencing for molecular diagnosis for the patients with familial HCM.

A novel <italic>Loss-of-function</italic> Mutation in <italic>MYBPC3</italic> Causes familial hypertrophic cardiomyopathy with extreme intrafamilial phenotypic heterogeneity

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

A novel  Mutation in  Causes familial hypertrophic cardiomyopathy with extreme intrafamilial phenotypic heterogeneity

Cardiomyopathies are a heterogeneous group of diseases predominantly affecting the heart muscle and often lead to progressive heart failure-related disability...

A novel Loss-of-function Mutation in MYBPC3 Causes familial hypertrophic cardiomyopathy with extreme intrafamilial phenotypic heterogeneity

Article Category: Original Article

Data publikacji: 01 mar 2023

Zakres stron: 71 - 78

DOI: https://doi.org/10.2478/bjmg-2022-0002

© 2022 Peng Y, Xu J, Wang Y, Zhao J, Zhang L, Chen Z, Jiang Y, Banerjee S, Zhang Z, Bai M, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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