Variants of the type II 3beta-hydroxysteroid dehydrogenase gene in children with premature pubic hair and hyperandrogenic adolescents.
To ascertain the potential role of heterozygosity for 3beta-hydroxysteroid (3beta-HSD) deficiency in children with premature pubic hair and adolescent girls with hyperandrogenism, we performed single-strand conformational polymorphism (SSCP) analysis of the 3beta-hydroxysteroid dehydrogenase type 2 (3beta-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 3beta-HSD2 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 3beta-hydroxysteroid dehydrogenase activity in three. Thus, 7 of 34 (20.6%) mildly hyperandrogenic patients carry heterozygous sequence variants of the 3beta-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.
Department of Pediatrics, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
S
S
Nayak
P A
PA
Lee
S F
SF
Witchel
D015065:17-Hydroxycorticosteroids / Q000097:blood; D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000595:Amino Acid Sequence; D000735:Androstenedione / Q000097:blood; D001940:Breast / Q000254:growth & development; D002648:Child; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006628:Hirsutism / Q000235:genetics; D006801:Humans; D017588:Hyperandrogenism / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009839:Oligomenorrhea / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011629:Puberty, Precocious / Q000235:genetics
D015065:17-Hydroxycorticosteroids; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases