A nonsense mutation in the LDL receptor gene leads to familial hypercholesterolemia in the Druze sect

• Published in: American journal of human genetics Vol. 50; no. 2; pp. 427 - 433
• Main Authors: LANDSBERGER, D, MEINER, V, RESHEF, A, LEVY, Y, VAN DER WESTHYZEN, D. R, COETZEE, G. A, LEITERSDORF, E
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.02.1992
• Subjects: ASIA; Base Sequence; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; CHOLESTEROL; CODONS; DEVELOPING COUNTRIES; DISEASES; Disorders of blood lipids. Hyperlipoproteinemia; DNA - genetics; DNA HYBRIDIZATION; DNA-ASE; ENDONUCLEASES; ENZYMES; ESTERASES; ETIOLOGY; GENE AMPLIFICATION; GENE MUTATIONS; genes; Genes, Dominant; Haplotypes; HEREDITARY DISEASES; HUMAN POPULATIONS; Humans; HYBRIDIZATION; HYDROLASES; HYDROXY COMPOUNDS; Hyperlipoproteinemia Type II - genetics; Islam; ISRAEL; lipoprotein (low density); Medical sciences; MEMBRANE PROTEINS; METABOLIC DISEASES; METABOLISM; MIDDLE EAST; Molecular Sequence Data; Mutation; MUTATIONS; NUCLEIC ACIDS; OLIGONUCLEOTIDES; ORGANIC COMPOUNDS; Pedigree; PHOSPHODIESTERASES; Polymerase Chain Reaction; POPULATIONS; PROTEINS; RECEPTORS; Receptors, LDL - genetics; STEROIDS; STEROLS 550200 > Biochemistry; Asia; Israel; Human; Lipoprotein LDL; Hypercholesterolemia; Sect; Family study; Nonsense mutation; Lipids; Metabolic diseases; Cholesterol; Genetic disease; Biological receptor
• ISSN: 0002-9297; 1537-6605

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the LDL receptor gene. Here we characterize an LDL receptor mutation that is associated with a distinct haplotype and causes FH in the Druze, a small Middle Eastern Islamic sect with a high degree of inbreeding. The mutation was found in FH families from two distinct Druze villages from the Golan Heights (northern Israel). It was not found neither in another Druze FH family residing in a different geographical area nor in eight Arab and four Jewish FH heterozygote index cases whose hypercholesterolemia cosegregates with an identical LDL receptor gene haplotype. The mutation, a single-base substitution, results in a termination codon in exon 4 of the LDL receptor gene that encodes for the fourth repeat of the binding domain of the mature receptor. It can be diagnosed by allele-specific oligonucleotide hybridization of PCR-amplified DNA from FH patients.