Screening for a prevalent LDL receptor mutation in patients with severe hypercholesterolaemia.

A rapid new method for the diagnosis of familial hypercholesterolaemia (FH) detects the deletion extending from intron 15 to exon 18 in the low density lipoprotein (LDL) receptor gene, i.e. the FH-Helsinki mutation responsible for a major portion of FH in Finland. Amplification of the DNA sequences flanking the deletion in the mutant allele generated an abnormal 391-bp product that could be detected by photographing the ethidium-bromide-stained agarose gel after electrophoresis. Up to 50 samples can be analysed in about 8 h. The method was validated by comparison with a routine Southern blot technique. The deletion was found in 23 out of 37 patients with a clinical diagnosis of FH (62%) and in 2 out of 73 with primary hypercholesterolaemia without a clinical diagnosis of FH within a series of 110 consecutive patients with severe hypercholesterolaemia (serum cholesterol greater than 8 mmol/l). The data indicate that DNA techniques may provide a supplementary aid for the routine diagnosis of FH and suggest that the polymerase chain reaction in particular may offer major advantages because of its simplicity and rapidity.