Copyright © 2003 by the European Society of Cardiology.
Clinical research
The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands
a Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands
b Department of Genetics and Cell Biology, University of Maastricht, Maastricht, The Netherlands
c Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
d Department of Clinical Genetics, Academic Hospital Maastricht, Maastricht, The Netherlands
e Department of Cardiology, Heart Lung Center Utrecht, Utrecht, The Netherlands
f Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
g Cardiovascular Disease in Women Charite and DHZB, Berlin, Germany
h Department of Experimental Cardiology, Max-Planck-Institute of Physiological and Clinical Research, Bad Nauheim, Germany
i Department of Experimental Cardiology, Academic Medical Centre, Amsterdam, The Netherlands
* Correspondence to: Dr M. Alders, Clinical Genetics, Academic Medical Centre, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands. Tel: +31 205665110; Fax: +31 206918626
E-mail address: m.alders{at}amc.uva.nl
Received 2 April 2003; revised 24 June 2003; accepted 3 July 2003
Abstract
Aims Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes that encode sarcomeric proteins. In this study we investigated the involvement of the sarcomeric myosin binding protein C in the Dutch HCM population.
Methods and results We initially screened 22 Dutch index patients for mutations in the MYBPC3 gene, which revealed four different mutations in 14 patients. The 2373insG mutation was identified in 10 apparently unrelated patients. A subsequent screening for the 2373insG mutation in a group of another 237 unrelated HCM patients revealed 50 additional carriers of the same genetic defect. Genotyping with polymorphic repeat markers and intragenic SNPs of the 60 Dutch as well as two German and five North American 2373insG carriers indicated they all share the same haplotype.
Conclusion The 2373insG mutation accounts for almost one-fourth of all HCM cases in the Netherlands (60/259), which is predominantly present in the northwestern part of the country (22/66) and is a founder mutation probably originating from the Netherlands.
Key Words: Hypertrophic • Cardiomyopathy • Myosin binding protein C • Founder mutation
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