SCREENING FOR KNOWN MUTATIONS IN THE LDL RECEPTOR GENE CAUSING FAMILIAL HYPERCHOLESTEROLEMIA

Familial hypercholesterolemia (FH) is caused by defective low density lipoprotein (LDL) receptors and is characterized by hypercholesterolem ia and premature coronary heart disease. Two strategies can be used to identify the mutation in the LDL receptor gene underlying FH. One str ategy is to search for novel mutations by DNA sequencing with or witho ut prior mutation screening. The other strategy is to screen for known mutations. In this study we employed the latter strategy to screen 75 unrelated, Norwegian FH subjects for 38 known mutations. Three of the 38 mutations were detected in our group of FH subjects, Two subjects had FH-Padova, one had FH-Cincinnati-2 and one had FH-Gujerat, When ad ditional unrelated FH heterozygotes were screened for the three mutati ons, the gene frequencies were 1.3%, 1.0% and 3.0%, respectively, In a ddition to identifying known mutations we also detected a novel stop c odon in codon 541 (S541X). We conclude that screening for known mutati ons in the LDL receptor gene should be used as a complementary strateg y to screening for novel mutations in order to understand the molecula r genetics of FH.