Molecular approaches for the diagnosis of 21-hydroxylase deficiency and congenital adrenal hyperplasia.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in deficiency of cortisol and aldosterone and overproduction of androgens. The 21-hydroxylase locus has a complicated structure, with a highly homologous pseudogene (CYP21P) and an active gene (CYP21) in tandem repeats, a high degree of interindividual variation in gene copy numbers, and exchange of sequences between CYP21P and CYP21. Nine mutations, representing sequences that are normally present in the pseudogene, account for about 95% of all affected CYP21 alleles. Accurate and rapid diagnostic evaluation of congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be performed by typing directly for disease-causing mutations using allele-specific polymerase chain reaction (PCR). A strong correlation exists between genotype and phenotype; mutational analysis can be used to predict disease severity in affected individuals.