A Chinese homozygote of familial hypercholesterolemia: identification of anovel C263R mutation in the LDL receptor gene

Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene; it is ch aracterized by a high concentration of LDL, which frequently gives rise to tendon xanthomas and premature coronary artery disease (CAD). Individuals w ith heterozygous FH in China often exhibit a milder phenotype than those in other countries. The diagnosis of heterozygous FH relies on the clinical p henotype and this does not always permit unequivocal diagnosis of the disea se. In the course of investigation of FH in a Chinese population sample, we found a family whose proband showed a markedly raised concentration of LDL cholesterol in plasma, and the presence of skin and tendon xanthomata. We used single-strand conformation polymorphism (SSCP) analysis to screen all the 18 exons and the exon-intron boundaries of the LDLR gene. One novel hom ozygous mutation, replacing T by C at nucleotide 850 in exon 6 was identifi ed. This change substituted cysteine for arginine at codon 263 (C263R) of t he LDLR. By means of mutant aIlele-specific amplification, we unequivocally diagnosed six heterozygotes with this novel mutation in the proband's fami ly.