Novel mutation of low density lipoprotein receptor gene associated with familial hypercholesterolemia

Objective To analyse the mutation of low density lipeprotein receptor (LDLR) gene associated with familial hypercholesterolemia (FH) and make a discussion on the relationship between genotype and phenotype. Methods The blood fat, electrocardiogram, heart and great vessels color Doppler were examined in propositus and family member. The promoter and all eighteen exons of LDLR gene were investigated by polymerase chain reaction (PCR),degenerate high performance liquid chromatogram (DHPLC) and DNA sequence analysis. The results were compared with the normal sequences in GenBank and FH database (www.ucl.uk/fh) to find the mutation. In addition,the apolipoprotein B100(ApoB100) gene for the known mutations(Q3500R) that cause familial defective ApoB100(FDB) was detected by directed screening.Results Two novel heterozygous c.1864 G→A (Asp622Asn) and c.1959 C→T(Val 653Val) mutations in the exon 13 of LDLR in promoter were detected. And Asp622Asn mutation segregated with the disease. No mutation Q3500R of ApeB100 was observed. Conclusions The heterozygous c.1864 G→A (Asp622Asn)mutation of LDLR gene is firstly determined in China. The heterozygous c.1864 G→A (Asp622Asn)mutation of LDLR gene is probably responsible for FH. Perhaps it is a particular pathogenesis for Chinese people. PCB-DHPLC could be used for detecting the mutation. Key words: Hypercholesterolemia; Receptors,LDL; Mutation