A "de-novo" Mutation In The Low Density Lipoprotein Recept Gene And The Function Of Its Associated Receptor

Background: Family hypercholesterolemia (FH) is a genetic disorder caused bymutations in the low density lipoprotein receptor (LDLR) gene, which may lead toimpaired ligand-receptor binding. Studies indicate that Epstein-Barr transformedlymphocytes (EBV-Ls) mirror LDLR activity of the cells in the body. Fluorescenceflow cytometry (FFC) represents a newer and less hazardous approach to functionalassessment of LDL ligand-receptor interaction.Objectives: The aim of this study is to construct EBV-Ls of heterozygous andhomozygous FH patients with a "de-novo" mutation Exon4 GAG683GCG in theLDLR gene causing an amino acid change from Glu to Ala, and then to determinethe function of its associated receptor.Methods: EBV-Ls were derived by using routine virus infection transform protocol.LDLR activity of the cells, which were incubated with fluorescently conjugatedDil-LDL and lipoprotein-depleted serum (LPDS), was measured by flowcytometry.Results: Three EBV-Ls were successfully derived and maintained for the patientswith homozygous, heterozygous FH and healthy control, respectively. The relativeLDLR expression in homozygous FH, heterozygous FH and healthy control were7.02%, 62.64% and 84.69%, respectively. So it is clear that the homozygous FHpatient's LDLR had an activity of 8.29% and the heterozygous FH patient's had anactivity of 73.96% as compared with the control.Conclusions: The cells data of "de-novo" LDLR gene mutation FH were preservedto keep with further studying. It is suggested that this mutation Exon4 GAG683GCGmay lead to the declining of LDLR activity in the patients with FH.