Lack of genotypephenotype correlation in congenital adrenal hyperplasia due to a CYP21A2-like gene.

[congenital adrenal hyperplasia]

Congenital Adrenal Hyperplasia (CAH ) due to 21 -hydroxylase deficiency , encoded by CYP 21 A 2 gene , is an autosomal recessive disorder . The CYP 21 A 2 gene , localized in a genetic unit defined RCCX module , is considered one of the most polymorphic of human genes .We considered new evidences about the presence of a RCCX trimodular haplotype with a CYP 21 A 2 -like gene to explain the lack of a genotype-phenotype correlation in individuals of two different families .To verify gene duplication we used Multiplex Ligation Probe-Dependent Amplifications (MLPA ) and to confirm the presence of a CYP 21 A 2 -like gene downstream TNXA gene we used previously described amplification and restriction strategy followed by the sequencing of the CYP 21 A 2 gene downstream TNXB gene .T he amplification strategy and restriction analysis of CYP 21 A 1 P /CYP 21 A 2 -TNXA PCR product in association with MLPA assay and sequencing of CYP 21 A 2 gene downstream TNXB were able to identify the presence of the CYP 21 A 2 -like gene in healthy subjects of the two families , wherein the direct sequencing of CYP 21 A 2 gene showed genotypes correlated to pathological phenotypes .The strategy suggested is useful to facilitate molecular testing in CAH patients , considering the new evidence about possible different haplotypes .