title: The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands. m.alders@amc.uva.nl
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.forename: Roselie
authors.initials: R
authors.lastname: Jongbloed
authors.forename: Wout
authors.initials: W
authors.lastname: Deelen
authors.forename: Arthur
authors.initials: A
authors.lastname: van den Wijngaard
authors.forename: Pieter
authors.initials: P
authors.lastname: Doevendans
authors.forename: Folkert
authors.initials: F
authors.lastname: Ten Cate
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Vosberg
authors.forename: Irene
authors.initials: I
authors.lastname: van Langen
authors.forename: Arthur
authors.initials: A
authors.lastname: Wilde
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.forename: Marcel
authors.initials: M
authors.lastname: Mannens
mesh_terms: D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009426:Netherlands; D010375:Pedigree; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C