Pseudogene/functional gene ratio in late-onset 21-hydroxylase-deficient adrenal hyperplasia

Late-onset adrenal hyperplasia caused by 21-hydroxylase deficiency leads to hyperandrogenic symptoms in 1% to 6% of hyperandrogenic women. Normally there are two 21-hydroxylase genes present in a 1:1 ratio. Gene CYP21A is a nonfunctional pseudogene, whereas CYP21B is an active gene. Abnormalities of the CYP21A/CYP21B gene ratio may serve as a marker for late-onset adrenal hyperplasia. Eight hyperandrogenic patients with late-onset adrenal hyperplasia and five control subjects were studied by evaluation of autoradiograms of Taq I and Kpn I digests by means of laser densitometry. Seven of eight (87%) patients with late-onset adrenal hyperplasia had an abnormal CYP21A/CYP21B gene ratio on laser densitometry, suggestive of CYP21A gene duplication, CYP21B gene deletion, or the conversion of a CYP21B gene to a CYP21A gene. One of the five control subjects had a heterozygous deletion of the CYP21A gene. The CYP21A/CYP21B gene ratio may serve as a useful genetic marker for late-onset adrenal hyperplasia in a non-high-risk population.