ClinVar

In classic cases of congenital adrenal hyperplasia due to 3-beta-HSD deficiency (201810) in 2 related families from the same village in eastern Switzerland, Rheaume et al. (1992) identified a G-to-A transition in exon 4 of both alleles, converting codon 171 (TGG) encoding trp into a TAG-stop codon (W171X). Mutation was predicted to result in a truncated protein of 169 amino acids (excluding the first met) instead of the normal 371 amino acids of the type II 3-beta-HSD protein. One of these families, extensively described by Zachmann et al. (1979), had severe salt-wasting. There was no virilization in the proposita. Her older brother died at the age of 4 weeks with clinical signs of a salt-losing crisis. He was incompletely masculinized and was found to have marked enlargement of the adrenals at autopsy. At puberty the proposita showed lack of spontaneous breast development and absence of a rise in serum estradiol following administration of human menopausal gonadotropin, thus suggesting that the defect was also present in the ovaries.