Functional characterization of LDL receptor missense variants located in the first cysteine-rich repeat in ligand binding domain of low density lipoprotein receptor

Abstract

Aim: Familial Hypercholesterolemia is an autosomal dominant disorder characterized by high blood cholesterol levels. With prevalence as high as 1 in 200 in some populations, FH is frequently underdiagnosed. FH is normally caused by mutations in the Low Density Lipoprotein Receptor (LDLR). Genetic screening for pathogenic LDLR mutations is a cost-effective approach to early diagnosis. However, with over 1700 observed LDLR mutations, distinguishing pathogenic mutations from benign mutations is a long-standing challenge in the field. In this study, we investigated the activity of three mutations located in the first cysteine- rich repeat of LDLR.