A Novel Nonstop Mutation in the Stop Codon and a Novel Missense Mutation in the Type II 3β-Hydroxysteroid Dehydrogenase (3β-HSD) Gene Causing, Respectively, Nonclassic and Classic 3β-HSD Deficiency Congenital Adrenal Hyperplasia

We investigated two novel point mutations in the human type II 3β-hydroxysteroid dehydrogenase (3β-HSD) gene causing a mild and a severe form of 3β-HSD deficiency congenital adrenal hyperplasia. The first is a nonstop mutation in the normal stop codon 373 of the gene in exon IV [TGA (Stop) → TGC (Cys) = Stop373C) identified from one allele of a female child with premature pubarche whose second allele had an E142K mutation. The Stop373C mutation predictably results in an open reading frame and a mutant-type (MT) II 3β-HSD protein containing 467 amino acid residues, compared with the 372 amino acid residues of wild-type (WT) protein. The second is a homozygous missense mutation in codon 222 [CCA (Pro) → ACT (Thr) = P222T] in the gene identified from a female neonate with salt-wasting disorder. The pcDNA vectors containing the constructs of WT II 3β-HSD cDNA, WT cDNA with the open reading frame (WT cDNA+), MT Stop373C with the open reading frame (Stop373C+) and MT P222T cDNA were transfected in COS-I and 293...