CONGENITAL ADRENAL-HYPERPLASIA DUE TO POINT MUTATIONS IN THE TYPE-II 3-BETA-HYDROXYSTEROID DEHYDROGENASE GENE

Classical 3-beta-hydroxysteroid dehydrogenase /DELTA-5-DELTA-4-isomerase (3-beta-HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads. We describe the nucleotide sequence of the two highly homologous genes encoding 3-beta-HSD isoenzymes in three classic 3-beta-HSD deficient patients belonging to two apparently unrelated pedigrees. No mutation was detected in the type I 3-beta-HSD gene, which is mainly expressed in the placenta and peripheral tissues. Both nonsense and frameshift mutations, however, were found in the type II 3-beta-HSD gene, which is the predominant 3-beta-HSD gene expressed in the adrenals and gonads, thus providing the first elucidation of the molecular basis of this disorder.