title: Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin.
abstract: South Africans of Indian origin have a high frequency of Familial Hypercholesterolemia (FH). Fibroblasts from a South African Indian FH homozygote, D, expressed about 30% of the normal number of LDL receptors. These receptors showed defective LDL binding. Sequence and haplotype analysis revealed that D had two different mutant LDL receptor alleles: FH Durban-1 is a point mutation [asp69(GAT) to tyr(TAT)] in ligand-binding repeat 2 and FH Durban-2 is a point mutation [glu119(GAG) to lys(AAG)] in ligand-binding repeat three of the LDL receptor. Single-strand conformational polymorphism analysis, which was used in the initial detection of these mutations, was also employed for subsequent population screening assays. These mutations were not detected in any of the South African Indian FH or hypercholesterolemic patients that were screened.
authors.affiliation: Department of Medical Biochemistry, University of Cape Town Medical School, South Africa.
authors.forename: D C
authors.initials: DC
authors.lastname: Rubinsztein
authors.forename: I
authors.initials: I
authors.lastname: Jialal
authors.forename: E
authors.initials: E
authors.lastname: Leitersdorf
authors.forename: G A
authors.initials: GA
authors.lastname: Coetzee
authors.forename: D R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D001483:Base Sequence; D005347:Fibroblasts / Q000378:metabolism; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000378:metabolism; D007194:India / Q000208:ethnology; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013019:South Africa
chemical_list: D011973:Receptors, LDL