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

Journal Article · Sat Feb 01 04:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:7014302

Landsberger, D; Meiner, V; Reshef, A; Leitersdorf, E ^[1]; Levy, Yishai ^[2]; Westhytzen, D.R. van der; Coetzee, G A ^[3]

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1. Hadassah University Hospital, Jerusalem (Israel)
2. Rambam Medical Center and Faculty of Medicine, Haifa (Israel)
3. University of Cape Town Medical School, (South Africa)

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the LDL receptor gene. Here the authors characterize and 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 either 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.

• OSTI ID: 7014302
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 50:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ASIA
CHOLESTEROL
CODONS
DEVELOPING COUNTRIES
DISEASES
DNA HYBRIDIZATION
DNA-ASE
ENDONUCLEASES
ENZYMES
ESTERASES
ETIOLOGY
GENE AMPLIFICATION
GENE MUTATIONS
HEREDITARY DISEASES
HUMAN POPULATIONS
HYBRIDIZATION
HYDROLASES
HYDROXY COMPOUNDS
ISRAEL
MEMBRANE PROTEINS
METABOLIC DISEASES
METABOLISM
MIDDLE EAST
MUTATIONS
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
POPULATIONS
PROTEINS
RECEPTORS
STEROIDS
STEROLS