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Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands
I Christiaans1, E A Nannenberg, D Dooijes
1Department of Clinical Genetics, Academic Medical Centre, Amsterdam, the Netherlands These authors contributed equally.
Insights
This review focuses on hypertrophic cardiomyopathy (HCM) founder mutations in the Netherlands, primarily in the MYBPC3 gene. It details three specific Dutch founder mutations and their implications for genetic testing and counseling.
Area of Science:
- Cardiovascular Genetics
- Genetic Epidemiology
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent autosomal dominant genetic disorder.
- Sarcomeric protein genes, particularly MYBPC3 and MYH7, are frequently implicated in HCM worldwide.
- Founder mutations significantly contribute to the genetic landscape of HCM in specific populations.
Purpose of the Study:
- To review Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients.
- To describe the genetics, genotype-phenotype correlations, prevalence, and distribution of MYBPC3 founder mutations in the Netherlands.
- To discuss the implications for genetic counseling and testing.
Main Methods:
- Literature review of existing studies on HCM and founder mutations in the Netherlands.
- Analysis of genetic data pertaining to MYBPC3 gene mutations in Dutch HCM patients.
- Synthesis of information on genotype-phenotype relationships, prevalence, and geographic distribution.
Main Results:
- The MYBPC3 gene harbors the majority of mutations in Dutch HCM patients.
- Three specific Dutch founder mutations in MYBPC3 (c.2373_2374insG, c.2864_2865delCT, c.2827C>T) are predominant.
- Detailed understanding of these mutations' genetic and clinical impact is crucial.
Conclusions:
- Founder mutations, particularly in MYBPC3, play a substantial role in HCM in the Netherlands.
- Understanding these specific mutations is essential for accurate genetic diagnosis and family screening.
- Genetic counseling and testing strategies should be tailored to the prevalence of these Dutch founder mutations.
Abstract:
In this part of a series on cardiogenetic founder mutations in the Netherlands, we review the Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients. HCM is a common autosomal dominant genetic disease affecting at least one in 500 persons in the general population. Worldwide, most mutations in HCM patients are identified in genes encoding sarcomeric proteins, mainly in the myosin-binding protein C gene (MYBPC3, OMIM #600958) and the beta myosin heavy chain gene (MYH7, OMIM #160760). In the Netherlands, the great majority of mutations occur in the MYBPC3, involving mainly three Dutch founder mutations in the MYBPC3 gene, the c.2373_2374insG, the c.2864_2865delCT and the c.2827C>T mutation. In this review, we describe the genetics of HCM, the genotype-phenotype relation of Dutch founder MYBPC3 gene mutations, the prevalence and the geographic distribution of the Dutch founder mutations, and the consequences for genetic counselling and testing. (Neth Heart J 2010;18:248-54.).
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