Repetitive sequences involved in the recombination leading to deletion of exon 5 of the low-density-lipoprotein receptor gene in a patient with familial hypercholesterolemia.

Alu sequences in the low-density-lipoprotein (LDL) receptor gene are suspected of being of importance for the creation of gene defects leading to familial hypercholesterolemia (FH). One potential mechanism is that Alu sequences undergo homologous recombination, producing deletions or duplications of DNA segments on genomic DNA. In at least four cases (FH626, PO, JA and FH-DK3), a deletion of exon 5 of the LDL receptor gene has been reported. Only one of these (FH626) have so far been characterized in detail by sequence analysis and shown to involve two of the Alu repeated sequences, which are present in introns 4 and 5. We here report the complete characterization of FH-DK3 and show that the cross-over break points involve sequences similar, but not at identical positions in the 5' end, to those reported for FH626. The recombinations in both FH-DK3 and FH626 are suggested to have occurred within a 22-bp repeated sequence found in both junction alleles.