Human Genetics

, Volume 92, Issue 6, pp 567–570

South African founder mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia in the Dutch population

  • J. C. Defesche
  • D. E. van Diermen
  • P. J. Lansberg
  • R. J. Lamping
  • P. W. A. Reymer
  • M. R. Hayden
  • J. J. P. Kastelein
Original Investigations

DOI: 10.1007/BF00420940

Cite this article as:
Defesche, J.C., van Diermen, D.E., Lansberg, P.J. et al. Hum Genet (1993) 92: 567. doi:10.1007/BF00420940

Abstract

In South African Afrikaners, three point mutations in the gene coding for the low-density lipoprotein (LDL)-receptor are responsible for more than 95% of the cases of familial hypercholesterolemia (FH). To investigate whether one or more of these mutations originated in The Netherlands, a large group of Dutch heterozygous FH patients was screened for the presence of these three mutations. Of these, a missense mutation in exon 9 of the LDL-receptor gene, resulting in a substitution of Met for Val408, responsible for 15% of FH in Afrikaners, was found in 19 (1.5%) of 1268 FH patients of Dutch descent. Nine of the patients carrying the exon 9 mutation on one allele shared the LDL-receptor DNA haplotype with an FH patient from South Africa, who was homozygous for the same mutation. This would suggest that the mutation in these patients and in the South African patient have a common ancestral background. The remaining ten FH patients all shared a common haplotype, partly identical to the Afrikaner haplotype, which chould have arisen from a single recombinational event. This mutation has not been described in persons other than of Dutch ancestry and supports the hypothesis that this mutation in exon 9 originated in The Netherlands and, in all likelihood, was introduced into South Africa by early Dutch settlers in the seventeenth century.

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • J. C. Defesche
    • 1
  • D. E. van Diermen
    • 1
  • P. J. Lansberg
    • 1
  • R. J. Lamping
    • 1
  • P. W. A. Reymer
    • 1
  • M. R. Hayden
    • 2
  • J. J. P. Kastelein
    • 1
  1. 1.Center for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada
  3. 3.Center for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, G1-114AZ AmsterdamThe Netherlands