ABSTRACT: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Unequal crossing over or gene conversion between the active CYP21A2 gene and the inactive CYP21A1P pseudogene accounts for 95% of mutations, but many non-pseudogene-derived mutations have been described. It is important for these new mutations to be assigned to a specific phenotype.
We report a young boy diagnosed with the classical simple virilizing phenotype in whom the CYP21A2 genetic analysis disclosed that he was a compound heterozygous for p.His38Leu and the c.290-13A/C>G mutations. The p.His38Leu mutation has been recently described, but has not been associated with a specific phenotype thus far. Residue 38 is the only charged amino acid of a hydrophobic patch that interacts closely with the membrane. This mutation leads to a non-charged amino acid, suggesting a much more hydrophobic continuous domain. This patch is highly conserved through different mammals indicating the importance of this domain in the protein-membrane interaction.
Our results support p.His38Leu as a severe mutation causing a classical simple virilizing phenotype.
Hormone Research in Paediatrics 09/2011; 76(3):214-7.