MUTATIONS IN THE TYPE-II 3-BETA-HYDROXYSTEROID DEHYDROGENASE GENE IN A PATIENT WITH CLASSIC SALT-WASTING 3-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY CONGENITAL ADRENAL-HYPERPLASIA

Inherited adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 b eta-HSD) deficiency is most likely caused by a mutation of the type II 3 beta-HSD gene. Cloning and sequencing of exons I-II, III, and IV an d portions of the adjacent introns, amplified by polymerase chain reac tion using primers specific for the type II gene, in one male pseudohe rmaphrodite with salt-wasting classic 3 beta-HSD deficiency congenital adrenal hyperplasia revealed the same mutation in all nine clones of exon IV consisting of a missense mutation at codon 248 [GTC (Val)-->AA C (Asn)] followed by a frameshift mutation at codon 249 [CGA (Arg)-->T A], resulting in a stop codon TAG, and normal sequences of exon I-II a nd III and the adjacent portions of introns. The same codon 248 and 24 9 mutations were found on one clone of his mother's DNA, but two other clones revealed normal sequences. These data indicate a homozygous co mbined missense/frameshift mutation in exon IV of the type II 3 beta-H SD gene resulting in severe salt-washing adrenal and gonadal 3 beta-HS D deficiency in the patient.