This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil.
In addition, the haplotype of CYP21 with chimera CYP21P/CYP21 causes 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH), while chimera TNXA/TNXB is associated with Ehlers-Danols syndrome as well as CAH.
This and most other mutations causing 21-hydroxylase deficiency are normally present in the CYP21P pseudogene and have presumably been transferred to CYP21 by gene conversion.
It has been demonstrated that one reaction for PCR amplification of the CYP21 gene and the chimeric CYP21P/CYP21 gene using mixed primers in combination with nested PCR and single-strand conformation polymorphism is considered highly efficient and accurate for molecular diagnosis of CAH due to 21-hydroxylase deficiency.
Correct diagnosis of 21-hydroxylase deficiency (21OHD) requires the identification of CYP21A2 gene deletions and CYP21A1P/CYP21A2 chimeric genes, which are disease-causing alleles, and gene duplications, which can lead to false-positive 21OHD allele results.
More than two hundred characterized 21-hydroxylase deficiency alleles appear to result exclusively from sequence exchanges involving the 21-hydroxylase gene (CYP21B) and a closely related pseudogene (CYP21A).
The presence of a highly homologous pseudogene, CYP21A1P, forms the basis for the relatively high incidence of 21- hydroxylase deficiency as deleterious sequences can be transferred from CYP21A1P to CYP21A2.