The diagnosis of non-classical (NC) 21-hydroxylase deficiency (21-OH-D) was substantiated by the finding of increased baseline and adrenocorticotropic hormone (ACTH)-stimulated 17-hydroxy-progesterone levels and was supported by molecular analyses of the CYP21A2 gene, which revealed V281L homozygosis in patient 1 and V281L/P30L compound heterozygosis in patient 2.
CYP21A2 mutations in Portuguese patients with congenital adrenal hyperplasia: identification of two novel mutations and characterization of four different partial gene conversions.
Therefore, these substitutions in synergism with the P30L mutation might decrease the enzyme activity resulting in a more severe phenotype, and a DNA sequence of -167 bases of the CYP21A2 gene should be performed in patients with 21-hydroxylase deficiency in whom the phenotype is more severe than predicted by the genotype.
The most frequent mutation in Romanian patients with 21-hydroxylase deficiency was I2G (43.9%), followed by deletions and large conversions (16.7%), I172N and the triple mutation (P30L+I2G+del8bp), accounting for 12.1% each, P30L (7.6%) and R356W (1.5%).