Molecular basis of familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic disease characterized by an elevated level of low density lipoprotein (LDL), xanthomas, and an increased frequency of heart attacks. One of the first descriptions of this disease was reported some 50 years ago by the Norwegian physician, Carl Müller. Research and clinical studies in the ensuing half century have shown that FH is caused by mutations in the gene for the LDL receptor. In this article, we review our studies of the last 5 years that have focused on the molecular genetics of the LDL receptor locus and its pathogenesis in FH.