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.
Nayak
S
S
Department of Pediatrics, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
Lee
P A
PA
Witchel
S F
SF
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