VARIANTS OF THE TYPE-II 3-BETA-HYDROXYSTEROID DEHYDROGENASE GENE IN CHILDREN WITH PREMATURE PUBIC HAIR AND HYPERANDROGENIC ADOLESCENTS

To ascertain the potential role of heterozygosity for SP-hydroxysteroi d (SP-HSD) deficiency in children with premature pubic hair and adoles cent girls with hyperandrogenism, we performed single-strand conformat ional polymorphism (SSCP) analysis of the 3 beta-hydroxysteroid dehydr ogenase type 2 (3 beta-HSD2) gene in 34 hyperandrogenic patients. Thre e sequence variants, two missense mutations and a 3'-UTR sequence vari ant, were detected among seven patients and in none of 100 healthy con trol subjects. One of these seven patients carried Leu(236) --> Ser on one 3 beta-HSD2 allele and Glu(318) --> STOP on one al-hydroxylase (C YP21) allele. ACTH stimulation tests were performed in 5/7 patients wi th sequence variants and were compatible with decreased 3 beta-hydroxy steroid dehydrogenase activity in three. Thus, 7 of 34 (20.6%) mildly hyperandrogenic patients carry heterozygous sequence variants of the 3 beta-HSD2 gene. Since obligate heterozygotic carriers for congenital adrenal hyperplasia are typically asymptomatic, other genetic or envir onmental influences may contribute to the expression of hyperandrogeni c symptoms in our patients. (C) 1998 Academic Press.