A new CYP21A2 nonsense mutation causing severe 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused primarily by defects in the steroid 21-hydroxylase gene (CYP21A2). The CYP21A2 gene is located in the HLA class III region on the short arm of chromosome 6p21.3, along with an inactive pseudogene, CYP21A1P, that is 98% homologous with CYP21A2 in its coding sequence. Most mutations found in the CYP21A2 gene are normally present in the pseudogene, implying that recombination events (microconversion) between these two genes may lead to the transfer of mutations from the pseudogene to the functional gene. Approximately only 5% of all CYP21A2 alleles causing disease harbour rare mutations not originating from the pseudogene. However, detection of these rare and spontaneous mutations has continued to expand worldwide. In this report, we describe the clinical and genetic findings in a Romanian newborn suffering from classic salt wasting form of CAH due to severe 21-hydroxylase deficiency.