[Relationship between changes in activities of low density lipoprotein receptor and gene mutation in familial hypercholesterolemia].

OBJECTIVE

To analyse the LDL receptor (LDLR) function and gene mutation in a familial hypercholesterolemia (FH) patient and illustrate the effects of gene mutation type on LDL receptor function.

METHODS

The pedigree of a FH proband was set up according to the serum lipid analysis and clinical presentations. The LDLR functions of cultured fibroblasts were investigated by radiolabelled ligand method. PCR-SSCP and DNA sequencing were performed on the genomic DNA isolated from whole blood

RESULTS

11 heterozygotes and 1 homozygote of FH were confirmed by pedigree analysis. The binding of LDL by LDLR of the proband was nearly normal while the uptake and degradation of LDL were only 3.6% and 1.7% as compared with controls. A frameshift mutation resulted from a G insert in codon 599 and a null mutation caused by CCA-->CCG base shift in codon 842 were found in exon 17.

CONCLUSION

A novel mutation of LDLR gene was reported. This mutation may severely affect the function of LDLR.