title: A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews.
abstract: 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.
authors.affiliation: Department of Internal Medicine B, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: V
authors.initials: V
authors.lastname: Meiner
authors.forename: D
authors.initials: D
authors.lastname: Landsberger
authors.forename: N
authors.initials: N
authors.lastname: Berkman
authors.forename: A
authors.initials: A
authors.lastname: Reshef
authors.forename: P
authors.initials: P
authors.lastname: Segal
authors.forename: H C
authors.initials: HC
authors.lastname: Seftel
authors.forename: D R
authors.initials: DR
authors.lastname: van der Westhuyzen
authors.forename: M S
authors.initials: MS
authors.lastname: Jeenah
authors.forename: G A
authors.initials: GA
authors.lastname: Coetzee
authors.forename: E
authors.initials: E
authors.lastname: Leitersdorf
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005006:Ethnicity; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D007585:Jews / Q000235:genetics*; D008097:Lithuania / Q000208:ethnology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*; D012016:Reference Values; D015183:Restriction Mapping; D014973:Xanthomatosis / Q000235:genetics
chemical_list: D015345:Oligonucleotide Probes; D011973:Receptors, LDL; D004247:DNA