Identification of deletions in the human low density lipoprotein receptor gene.

DNA samples from 70 unrelated UK patients with heterozygous familial hypercholesterolaemia were screened by Southern blot hybridisation with a 5' fragment of the human low density lipoprotein (LDL) receptor cDNA. In the majority of cases, the restriction fragment pattern of the LDL receptor gene was indistinguishable from that observed in normal subjects. However, three patients were found to have a deletion of approximately 1 kb in the central portion of the gene. Mapping experiments indicated that in two patients a similar deletion has occurred that includes all or part of exon 5, and in the third patient a deletion has occurred that includes exon 7. Taking into account our previously described patient with a deletion in the 3' part of the gene, this means that in four out of 70 UK patients with familial hypercholesterolaemia (6%), the defect is caused by a detectable deletion of part of the coding portion of the low density lipoprotein receptor gene.