Abstract 25

Over the last decade, premature pubarche due to 3β-HSD deficiency was reported in a high frequency (1.5-13%) based on elevated Δ5 steroid levels. However several molecular studies found no mutation in type I and II 3β-HSD genes in these patients, suggesting that a mutant 3β-HSD gene is not the cause of this disorder. We screened the presence of mutations in the type 3β-HSD gene in 8 girls with premature pubarche, who fulfilled hormonal criteria for 3β-HSD deficiency. The mean age of pubarche was 5.6 years, ranging from 3-7. All patients had Tanner stage II-III pubic hair, except one girl who had Tanner IV. Only one girl had breast development at 8.6 years. two girls had advanced bone age and two facial acne. One patient showed mild clitoral enlargment (2.0×0.9cm). None of the patients had a history of salt-losing, consanguinity or affected siblings. Genomic DNA was used as template to amplify the coding sequence of the type II gene by PCR, and screened for mutations by denaturing gradient gel electrophoresis (DGGE). Manual sequencing was done using the dideoxy nucleotide chain termination method. ACTH-stimulated 17-hydroxyprogesterone was normal and 17-hydroxypregnenolone (17Preg) was elevated. Six patients showed no mutations in type II 3β-HSD by DGGE, whose ACTH-stimulated 17Preg ranged from 7 to 21 SD above the normal mean levels for pubertal stage-matched subjects. A homozygous T259M and a new compound heterozygous G129R and P222H mutations were found in the type II 3β-HSD gene in two girls whose ACTH-stimulated 17Preg levels were 9 and 72 SD above the normal mean level, respectively. We conclude that 3β-HSD deficiency due to mutations in the type II 3β-HSD gene can present as PP in girls, and ACTH-stimulated 17Preg levels might overlap in those patients with and without mutation.