The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands.
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.
Alders
Marielle
M
Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands. m.alders@amc.uva.nl
Jongbloed
Roselie
R
Deelen
Wout
W
van den Wijngaard
Arthur
A
Doevendans
Pieter
P
Ten Cate
Folkert
F
Regitz-Zagrosek
Vera
V
Vosberg
Hans Peter
HP
van Langen
Irene
I
Wilde
Arthur
A
Dooijes
Dennis
D
Mannens
Marcel
M
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
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C