MUTATION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-II ASSOCIATED WITH PSEUDOHERMAPHRODITISM IN MALES AND PREMATURE PUBARCHE OR CRYPTIC EXPRESSION IN FEMALES

A mutation (A82T) is described in the coding sequence of the gene for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) type II that is assoc iated with variable clinical consequences. Four homozygotes are descri bed, all of which showed elevated levels of Delta(5) steroids consiste nt with 3 beta-HSD deficiency. Two males from a consanguineous family were found to be homozygous for A82T and were affected with pseudoherm aphroditism. They differed in their degree of mild salt loss. In the s ame family a female was found to be homozygous for A82T, but was clini cally normal and had no history of premature pubarche or of abnormal m enstrual cycles. However, in an apparently unrelated family, the A82T mutation was found in a female affected with premature pubarche. This is the first report of a proven mutation in 3 beta-HSD type II associa ted with premature pubarche.