The codon 213 of the 11 beta-hydroxysteroid dehydrogenase type 2 gene is ahot spot for mutations in apparent mineralocorticoid excess

In the kidney, the 11 beta-hydroxysteroid dehydrogenase type 2 enzyme (11 b eta HSD2) inactivates glucocorticoids to their inactive ketoforms and thus prevents endogenous glucocorticoids from occupying the nonselective mineral ocorticoid receptor in epithelial tissues. Several mutations have been desc ribed in the 11 beta HSD2 gene in the congenital syndrome of apparent miner alocorticoid excess. These mutations generate partially or completely inact ive 11 beta HSD2 enzymes. In the present work, we describe an already known mutation in a new patient affected by apparent mineralocorticoid excess, which results in an arginin e-to-cysteine mutation (R213C) in the 11 beta HSD2 enzyme. This mutation ha s been found in two other independent families. In vitro expression studies of this mutant provide evidence that the mutant protein is normally expres sed, but its activity is abolished. The CGC-to-TGC (C-toT) transition at co don 213 can be considered a typical CpG-consequence mutation. The present finding suggests that the codon R213 of 11 beta HSD2 is a hot s pot for mutations in this gene, as shown by the occurrence of an R213C poin t-mutation in several families unrelated to each other.