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Objective: To investigate low density lipoprotein receptor (LDLR) function and gene mutation in Chinese patients with familial hypercholesterolemia(FH)., Methods: Lymphocytes were isolated from 10 ml anticoagulated peripheral blood of the patients, then a flow-cytometric method (FCM) with 1,1'-dioctadecyl-3,3,3', 3-tetramethylindocarbocyanine perchlorate labelled low density lipoproetin (DiI-LDL) was used to identify the function of LDLR on the surface of lymphocytes. Genomic DNA was isolated from whole blood of FH patients and analyzed by PCR-single strand conformation polymorphism (SSCP) and nucleotide sequencing methods., Results: Defects of binding and uptaking of LDLR were identified by FCM in 2 FH patients in one family, and their parents were examined in the present study. Then they were analyzed genetically. The detected mutation was a deletion of A, which caused a frame shift in codon 297 of exon 6 and introduced a beforehand stop codon in codon 369., Conclusion: A novel mutation of LDL receptor gene was detected by the combination of FCM and PCR-SSCP methods.

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.