IDENTIFICATION OF THE 408-VALINE TO METHIONINE MUTATION IN THE LOW-DENSITY-LIPOPROTEIN RECEPTOR IN A GERMAN FAMILY WITH FAMILIAL HYPERCHOLESTEROLEMIA

Familial hypercholesterolemia (FH) is caused by different mutations in the gene encoding the low density lipoprotein receptor (LDLR). In Cau casian patients, at least three single point mutations have been ident ified causing FH. The asparagine206 to glutamine, and valine408 to met hionine mutations were originally described in Afrikaners and recently identified in Dutch FH patients. The proline664 to leucine mutations was previously identified in an FH homozygote of Asian Indian origin a nd later identified in patients from London. Any of these mutations ca n be identified using direct amplification of genomic DNA by the polym erase chain reaction (PCR) and restriction enzyme digestion of PCR pro ducts. In this study, 100 unrelated German FH patients were screened f or these three mutations. The valine408 to methionine mutation was ide ntified in one individual and subsequently in the hypercholesterolemic child of the proband. Haplotype analysis with 7 restriction fragment length polymorphisms (RFLPs) revealed that the mutant allele carried t he same haplotype as the previously described patients in South Africa and the Netherlands. Our finding supports the previous assumption of the European origin of the mutation.