Genes, pseudogenes and like genes: the case of 21-hydroxylase in Italian population

Recently, we have considered two new findings in genetics of 21-hydroxylase deficiency with great interested: the existence of rare RCCX trimodular haplotypes, where the CYP21A2 like-gene downstream of the TNXA gene carries from one to six pseudogene mutations, and population specific allelic frequencies of wild-type CYP21A2 loci in the CYP21A1P pseudogene. Both these events represent a further complication in CYP21A2 genetics. Therefore, the choice of the molecular protocol becomes a crucial point when genetic analysis is required. In this regard, we must consider that the literature is still lacking consistent data on the Italian population. For this reason, we report genetic results obtained on 375 healthy individuals of Italian origin.

Different genetic protocols were compared and novel molecular strategies were performed.

In our group, only two known haplotypes were identified. In addition, specific allelic frequencies of CYP21A2 wild-type loci in the pseudogene have been established.

Based on our results, we can affirm that the employment of different molecular methods is necessary to ensure a correct CYP21A2 genotyping. In order to avoid mistakes both in patient diagnosis and/or in risk evaluation of the relatives, each case should be investigated in function of a careful clinical evaluation and the molecular test should be performed in specialized centres.