Identification of a mutation, N543H, in exon 11 of the low-density lipoprotein receptor gene in a French family with familial hypercholesterolemia

The low-density lipoprotein receptor (LDLR) is a transmembrane glycoprotein that supplies cells with cholesterol through LDL endocytosis. LDLR gene mutations lead to familial hypercholesterolemia (FH), a disease inherited in an autosomal dominant fashion with a frequency of about 1/500 in the general population. More than 180 mutations of the receptor gene have already been identified. We have screened six restriction fragment length polymorphism (RFLP) alleles in 15 well-characterized FH families, according to the criteria of the EAS Group Study and in 26 healthy unrelated subjects from the same area (Grenoble, France). In one family, we found an unusual restriction pattern with the enzyme NcoI that cosegregated with the disease. This abnormality led us to identify a new mutation that creates an additional restriction site for this enzyme.