Variants of the type II 3β-hydroxysteroid dehydrogenase gene in children with premature pubic hair and hyperandrogenic adolescents

To ascertain the potential role of heterozygosity for 3β- hydroxysteroid (3β-HSD) deficiency in children with premature pubic hair and adolescent girls with hyperandrogenism, we performed single-strand conformational polymorphism (SSCP) analysis of the 3β-hydroxysteroid dehydrogenase type 2 (3β-HSD2) gene in 34 hyperandrogenic patients. Three sequence variants, two missense mutations and a 3'-UTR sequence variant, were detected among seven patients and in none of 100 healthy control subjects. One of these seven patients carried Leu²³⁶ → Ser on one 3βHSD2 allele and Glu³¹⁸ → STOP on one 21-hydroxylase (CYP21) allele. ACTH stimulation tests were performed in 5/7 patients with sequence variants and were compatible with decreased 3β-hydroxysteroid dehydrogenase activity in three. Thus, 7 of 34 (20.6%) mildly hyperandrogenic patients carry heterozygous sequence variants of the 3β-HSD2 gene. Since obligate heterozygotic carriers for congenital adrenal hyperplasia are typically asymptomatic, other genetic or environmental influences may contribute to the expression of hyperandrogenic symptoms in our patients.