In vitro functional characterization of missense mutations in the LDLR gene

Background: Mutations in the LDL receptorgene are the major cause of familial hypercholesterolaemia (FH) but it has been previously shown that the simple finding of a variation in the coding sequence of the LDLR does not confirm that it is the actual cause of FH. The pathogenicity of five missense alterations in the LDLR gene coding sequence found in a previous epidemiologic study was investigated. Methods: The effects of the different sequence variants on LDLR expression and activity were analysed in vitro stably transfected CHO-ldlA7 cells by immunobloting of cell extracts, by uptake and degradation rates of 125 I-labelled LDL and immunofluorescence microscopy of whole cells. Analysis in silicowas also