Deletions of the low density lipoprotein receptor gene underlying familial hypercholesterolaemia: screening by polymerase chain reaction using pooled DNA and blood samples.

We evaluated the feasibility of methods based on the polymerase chain reaction (PCR) and non-automated or automated gel electrophoresis to detect clinically important DNA deletions in pooled DNA and blood samples. Two common low density lipoprotein (LDL) receptor mutations causing familial hypercholesterolaemia (FH) in the Finnish population were easily identified in pools corresponding to 20 individuals. One of these mutations (FH-North Karelia) deletes seven nucleotides from exon 6 of the LDL receptor gene. PCR amplification of DNA samples from the heterozygous patients with the FH-North Karelia gene results in the formation of DNA heteroduplexes, which markedly improves mutation detection. These studies show the applicability of semi-automated PCR techniques in the screening of DNA deletions and demonstrate the clinical diagnostic usefulness of heteroduplex formation.