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Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

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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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    I. A. W. van Rijsingen

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  1. I. A. W. van Rijsingen
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  2. J. F. Hermans-van Ast
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  3. Y. H. J. M. Arens
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  4. S. M. Schalla
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  5. C. E. M de Die-Smulders
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  6. A. van den Wijngaard
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  7. Y. M. Pinto
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Correspondence to I. A. W. van Rijsingen.

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Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands

Departments of Cardiology and Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands

Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands

Department of Molecular Genetics, Maastricht University Medical Center, Maastricht, the Netherlands

Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands

I.A.W van Rijsingen Department of Cardiology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands

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van Rijsingen, I.A.W., Ast, J.F.Hv., Arens, Y.H.J.M. et al. Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?. NHJL 17, 458–463 (2009). https://doi.org/10.1007/BF03086304

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