Functional studies of CYP21A2 mutants complement structural and clinical predictions of disease severity in CAH

摘要

Mutations in the steroid 21-hydroxylase gene (CYP21A2) are the most common cause of congenital adrenal hyperplasia (CAH). In classic CAH [salt-wasting (SW), simple virilizing (SV)], affected children present with or without salt-loss during the neonatal period, accelerated growth during childhood, and affected girls are born virilized. In mild nonclassic (NC) CAH, the most common symptoms are premature puberty, hirsutism and menstrual irregularities in young women, while adult men are assumed to be asymptomatic. Diagnosis is established by serum measurements of 17-hydroxyprogesterone (17OHP) and 21-deoxy corti-sol basally and after an ACTH challenge.1 Genotyping offers a valuable complement to biochemical tests in the diagnostics of CAH. Nine pseudogene-derived mutations account for most of the affected CYP21A2 alleles.