Mutations in the type II 3β-hydroxysteroid dehydrogenase gene in a patient with classic salt-wasting 3β-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia

Inherited adrenal and gonadal 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency is most likely caused by a mutation of the type II 3β-HSD gene. Cloning and sequencing of exons I-II, III, and IV and portions of the adjacent introns, amplified by polymerase chain reaction using primers specific for the type II gene, in one male pseudohermaphrodite with salt-wasting classic 3β-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) → AAC (Asn) followed by a frameshift mutation at codon 249 [CGA (Arg)→ TA], resulting in a stop codon TAG, and normal sequences of exon I-II and III and the adjacent portions p of introns. The same codon 248 and 249 mutations were found on one clone of his mother’s DNA, but two other clones revealed normal sequences. These data indicate a homozygous combined missense/frameshift mutation in exon IV of the type II 3β-HSD gene resulting in severe salt-wasting adrenal and gonadal 3β-HSD deficiency in the patient.