Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands

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.).

Keywords: Cardiomyopathy; Founder Effect; Mutation; Myosin-binding Protein C.

Figure 1

Distribution of the c.2373­_2374insG mutation (A), the c.2827C>T mutation (B) and the c.2864_2865delCT mutation (C). Different colours refer to the number of patients with the mutation per 1,000,000 inhabitants in a specific postal code area. Between brackets the number of postal code areas.

Figure 2

Disease penetrance in 301 HCM mutation carriers with different types of mutations in the MYBPC3 gene.