Background. Familial hypercholesterolemia is one of the most frequent hereditary metabolic diseases. As a result of the functional disorder of the molecule of the LDL receptor LDL cholesterol is not sufficiently eliminated from the blood stream and exerts an atherogenic effect. The objective of the study was to introduce direct detection of mutations in the gene for the LDL receptor and characterize the spectrum of mutations in the Czech population. Methods and Results. The authors analyzed a group of 84 unrelated patients where on the basis of clinical and biochemical criteria the diagnosis of FH was established. From the group 12 patients were eliminated (14.3 %) where a mutation 3500 in the gene for apolipoprotein (apo) B-100 was detected. This mutation is most frequently the cause of a familial defect of apo B-100 (FDB), which cannot be differentiated clinically or biochemically from FH. In the LDL receptor gene a total of 11 mutations were found in 14 unrelated patients (16.7 %), incl. 7 mutations not described hitherto. Conclusions. This is the first systematic characteristic of the spectrum of mutations in the LDL receptor gene in the Czech population. Molecular genetic analysis of the gene for the LDL receptor in affected families can contribute towards early assessment of the diagnosis of FH and thus to prevention of life threatening cardiovascular episodes in asymptomatic subjects.

        Key words: LDL receptor, apolipoprotein B-100, mutation, familial hypercholesterolemia, familial defective apolipoprotein B-100, atherosclerosis.