DEFECTS IN THE HSD11 GENE ENCODING 11-BETA-HYDROXYSTEROID DEHYDROGENASE ARE NOT FOUND IN PATIENTS WITH APPARENT MINERALOCORTICOID EXCESS OR11-OXOREDUCTASE DEFICIENCY

The syndrome of apparent mineralocorticoid excess (AME) is a form of l ow renin hypertension that is thought to be caused by congenital defic iency of 11beta-hydroxysteroid dehydrogenase (11HSD) activity. This en zyme converts cortisol to cortisone and apparently prevents cortisol f rom acting as a ligand for the mineralocorticoid (type 1) receptor. It also catalyzes the reverse oxoreductase (cortisone to cortisol) react ion. Four patients with AME and the parents of the first patient descr ibed (now deceased) were analyzed for mutations in the cloned HSD11 ge ne encoding an 11HSD enzyme. A patient with suspected cortisone reduct ase deficiency was also studied. No gross deletions or rearrangements in the HSD11 gene were apparent on hybridizations of blots of genomic DNA. Direct sequencing of polymerase chain reaction-amplified fragment s corresponding to the coding sequences, intronexon junctions, and pro ximal untranslated regions of this gene revealed no mutations. AME may involve mutations in a gene for another enzyme with 11HSD activity or perhaps another cortisol-metabolizing enzyme.