The molecular basis of a hereditary form of hypertension, glucocorticoid-remediable aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary cause of human hypertension in which aldosterone secretion is regulated by ACTH. Recent studies demonstrate that this disorder is caused by fusion of regulatory sequences of the steroid 11 β-hydroxylase gene to coding sequences of the aldosterone synthase gene. These mutations occur by unequal crossing over between these two genes and result in ectopic expression of aldosterone synthase in adrenal fasciculata. These features explain the physiology and genetics of GRA and provide the basis for a simple direct genetic test for this disorder.