Identification of novel CYP21A2 mutations in patients with 21-hydroxylase deficiency

Abstract

The laboratory of Human Molecular Genetics at CBMEG-UNICAMP in association with the Pediatric Endocrinology group at the Department of Pediatrics - FCM and also with the Department of Endocrinology at the FMRP-USP, is developing a research on mutation identification and characterization in the CYP21A2 gene responsible for Congenital Adrenal Hiperplasia (CAH) due to 21-hydroxylase deficiency. Normally, CYP21A2 affected alelles bear gene deletions, conversions or one (or more) of 9 pseudogene-originated point mutations (microconversions). Those are frequent mutational events due to the presence of a pseudogene (CYP21A1P). However, there are disease-causing mutations that are not originated in the CYP21A1P and they are considered as new mutations. In our studies we have identified 10 new mutations in patients with 21-hydroxylase deficiency. In general, new mutations had been identified in alelles with none pseudogene-originated mutation. However, in one case a new mutation was identified in association with a pseudogene-originated mutation. In this in case there was a divergence between the genotype and phenotype. The objective of the present project is to study 24 families with CAH affected individuals due to 21-hydroxylase deficiency in which the genotypes and phenotypes are divergent with only the analysis of the pseudogene-originated mutation. Therefore, in these cases sequencing the gene if is necessary for verification of other possible mutations.