IDENTIFICATION OF A NOVEL MUTATION IN EXON-13 OF THE LDL RECEPTOR GENE CAUSING FAMILIAL HYPERCHOLESTEROLEMIA IN 2 SPANISH FAMILIES

DNA from 30 unrelated Spanish patients with familial hypercholesterole mia (FH) was studied by single-strand conformation polymorphisms (SSCP )/heteroduplex analysis for mutation detection in exon 13 of low densi ty lipoprotein (LDL) receptor gene. Two patients were found to have an abnormal pattern by heteroduplex analysis, and direct sequencing reve aled a C to G substitution at nucleotide position 1965, that results i n a Phe to Leu change in codon 634, F634L. We have developed a PCR bas ed assay to detect this mutation in family members. We found three add itional F634L mutation carriers, and all of them had high cholesterol levels. Haplotype analysis revealed that all F634L mutation carriers h ad the same allele determined by TaqI -, StuI +, AvaII +, NcoI -, sugg esting the presence of a common ancestor. We report a novel mutation l ocated in exon 13 of the LDL receptor gene that causes FH. We also dem onstrate the importance of combining SSCP and heteroduplex analysis to improve mutation detection.