Mutation analysis in familial hypercholesterolemia patients of different ancestries: identification of three novel LDLR gene mutations.
Twelve familial hypercholesterolemia (FH) patients of different ancestries living in South Africa were subjected to mutation analysis of the low-density lipoprotein receptor (LDLR) gene. Nine different mutations were identified in 10 patients. Six of these, including the founder-related mutation C660X identified in two Lebanese patients, have previously been described in other FH patients with compatible genetic backgrounds, and/or in patients originating from countries where admixture is not uncommon. Characterization of an abnormal electrophoresis pattern detected in exon 4 of the LDLR gene by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, revealed a novel G deletion at codon 185 (617delG) which resulted in a downstream stop codon. Two of the new mutations identified resulted in amino acid substitutions and were designated R57C and Q357P.
Callis
M
M
Department of Human Genetics, Faculty of Health Sciences, University of the Orange Free State, Bloemfontein, South Africa.
Jansen
S
S
Thiart
R
R
de Villiers
J N
JN
Raal
F J
FJ
Kotze
M J
MJ
D001055:Apolipoproteins B / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011973:Receptors, LDL / Q000235:genetics*; D017384:Sequence Deletion; D013019:South Africa
D001055:Apolipoproteins B; D011973:Receptors, LDL