Detection of LDL-receptor gene mutation causing familial hypercholesterolemia in Croatia

Familial hypercholesterolemia (FH) is a monogenic, autosomal dominant disease caused by functional mutation in the low density lipoprotein (LDL) receptor gene. This work presents a part of systematic study of molecular basis of hypercholesterolemia in Croatia. The study included 420 hypercholesterolemic subjects with total cholesterol and LDl-cholesterol values of more than 6, 7 mmol/L and more than 4, 9 mmol/L, respectively, and an equal number of healthy controls. The presence of molecular changes in exon 4 of the LDL-receptor gene was examined by the single strand conformation polymorphism (PCR-SSCP) method and direct automated sequencing and was confirmed by restriction fragment length polymorphism (PCR-RFLP) method. Mutation C127R was identified in one patient and has not been reported previously. It caused conformational changes of the ligand binding domain of the LDL-receptor and was dimished receptor activity, too. Mutation D200G was identified in two patients and was previously described as FH-Padova. In addition to clinical application, results of this study contribute to establishment of the gene map of risk factors for atherosclerosis in Croatia.