FAMILIAL LIGAND-DEFECTIVE APOLIPOPROTEIN B-100 - SIMULTANEOUS DETECTION OF THE ARG(3500)-]GLN AND ARG(3531)-]CYS MUTATIONS IN A FRENCH POPULATION

Familial ligand-defective apolipoprotein B-100 (FDB) is an autosomal d ominant disorder leading to plasma LDL cholesterol elevation and coron ary artery disease (CAD). Two specific mutations in the APOB gene-R350 0Q and R3531C-induce FDB. We report an original method to detect both mutations simultaneously, based upon PCR-mediated, site-directed mutag enesis and double restriction of a unique PCR product. With this metho d we have investigated the prevalence of these mutations in 1,040 Fren ch patients. The R3500Q8 mutation was found in five probands, Genotype s were determined for 10 APOB polymorphic markers and were consistent with the common European ancestral haplotype previously reported. The only exception was one FDB proband who did not harbor the 48 repeat al lele of the 3'HVR. Additionally, the first two R3531C mutations were i dentified in French probands. Genotypes were consistent with a previou sly reported haplotype, suggesting that this is another mutation of Eu ropean ancestry. (C) 1997 Wiley-Liss, Inc.