A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews.

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density-lipoprotein (LDL) receptor.Here we characterize an LDL-receptor founder mutation that is associated with a distinct LDL-receptor haplotype and is responsible for FH in 35% of 71 Jewish-Ashkenazi FH families in Israel.Sixty four percent (16/25) of the Ashkenazi patients who carry this mutant allele were of Lithuanian origin.The mutation was not found in 47 non-Ashkenazi FH families.This mutation was prevalent (8/10 FH cases) in the Jewish community in South Africa, which originated mainly from Lithuania.The mutation, a 3-bp in-frame deletion that would result in the elimination of Gly197, has been previously designated FH-Piscataway.PCR amplification of a DNA fragment that includes the mutation in heterozygous individuals results in the formation of a heteroduplex that can be demonstrated by PAGE and used for molecular diagnosis.