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.
Department of Human Genetics, Faculty of Health Sciences, University of the Orange Free State, Bloemfontein, South Africa.
M
M
Callis
S
S
Jansen
R
R
Thiart
J N
JN
de Villiers
F J
FJ
Raal
M J
MJ
Kotze
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