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Updated: Jun 16, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest
I A W van Rijsingen1, J F Hermans-van Ast, Y H J M Arens
1Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.
Insights
Double-heterozygous mutations in hypertrophic cardiomyopathy (HCM) genes like MYH7 and CSRP3 can cause severe disease. Cardiologic screening, including NT-proBNP, is crucial for families with unexplained HCM phenotypes.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Diagnostics
Background:
- Advancements in genetic testing increasingly identify double-heterozygous mutations.
- Double heterozygosity contributes to the clinical variability observed in hypertrophic cardiomyopathy (HCM) families.
Purpose of the Study:
- To investigate the clinical implications of double-heterozygous mutations in a family with hypertrophic cardiomyopathy.
- To highlight the role of genetic screening and cardiological assessment in managing HCM.
Main Methods:
- Described a family with members carrying single or double heterozygous mutations in MYH7 and CSRP3 genes.
- Evaluated clinical phenotypes and emphasized cardiological screening protocols.
Main Results:
- Double-heterozygous mutations were associated with a more severe clinical phenotype in the studied family.
- NT-proBNP was identified as a potential supplementary diagnostic tool in cardiological screening.
Conclusions:
- Consider double-heterozygous mutations in families presenting with severe, unexplained HCM.
- Recommend comprehensive cardiological screening and extended genetic evaluation for all family members, even if a single mutation is identified.
Abstract:
Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We describe a family in which members carry either a single mutation or are double heterozygous for mutations in myosin heavy chain gene (MYH7) and cysteine and glycine-rich protein 3 (CSRP3). The described family emphasises the idea of a more severe clinical phenotype with double-heterozygous mutations. It also highlights the importance of cardiological screening where NT-proBNP may serve as an added diagnostic tool.Conclusion. With a more severe inexplicable phenotype of HCM within a family, one should consider the possibility of double-heterozygous mutations. This implies that in such families, even when one disease-causing mutation is found, all the family members still have an implication for cardiological screening parallel to extended genetic screening. (Neth Heart J 2009;17:458-63.).
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