Mutational Characterization of Steroid 21-Hydroxylase Gene in Portuguese patients with Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common inherited disorder of adrenal hormone biosynthesis due to mutations in the 21-hydroxylase gene, CYP21A2. Genotyping for ten of the most frequent mutations was performed in 84 Portuguese CAH patients: 10 salt-wasters, 6 simple-virilizers and 68 non-classical patients. The patients were diagnosed by a level of 17-hydroxyprogesterone above 10 ng/ml either in basal conditions or after an ACTH 0,25 mg IV Test. A variety of genotyping techniques were used to detect these ten mutations. CYP21A2 mutations were detected in 91.7% (77/84) of the patients. The frequency of alleles carrying two or more CYP21A2 mutations (9.5% - 16/168) is higher than in other populations. The most frequent mutations identified in our population were V281L (41.7%) and deletions/conversions involving the promoter region of the CYP21A2 gene (28.3%). A decreased frequency of IVS2-12C/A > G mutation (5.6%) was the most characteristic feature of our population. This study allow the characterization of the mutational spectrum of CAH patients, mainly non-classical CAH, with 21-hydroxylase deficiency from Portugal showing specific genetic features of this population which reveals differences with worldwide countries.