Identification of the recombination site within the steroid 21-hydroxylase gene (CYP21) of the HLA-B47,DR7 haplotype.

The HLA haplotype A3-Cw6-B47-C4A91-BQ0-DR7 is associated with congenital adrenal hyperplasia (CAH), since it only carries the dysfunctional steroid 21-hydroxylase A pseudogene as well as the 5' adjacent complement C4A gene. The recombination site leading to the deletion of the complement C4B and steroid 21-hydroxylase B genes in this haplotype was studied by determining the 21-hydroxylase genomic DNA sequence in comparison to the standard CYP21A- and CYP21B-specific sequences. A 200-bp region between exons 7 and 8 was identified as a possible recombination site. Thus the deleted area comprises the 3' end of the CYP21A pseudogene, the entire C4B gene and the 5' end of the CYP21B gene. The findings were confirmed by PCR amplification of a 1.8-kb fragment of the CYP21 gene. This PCR system is specific for CYP21A/B recombinant genes and may be used for screening among CAH patients carrying this type of deletion.