title: A multicenter study of women with nonclassical congenital adrenal hyperplasia: relationship between genotype and phenotype.
abstract: Characteristic presentation of nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency was compared between women carrying a severe and a mild CYP21 mutation (Group 1, N = 26) versus homozygotes for mild mutations (Group 2, N = 8). The diagnosis was based on elevated ACTH-stimulated 17OH-progesterone (17OHP). Genotyping for 10 mutations was performed by PCR-based techniques. Jewish patients predominated among Group 2 (25% vs 11.5% in Group 1); however, 85% of all patients were non-Jewish Caucasians. Average age of presentation was 23-25 years, and did not differ between groups. Hirsutism, and to a lesser extent oligomenorrhea and acne, were more prevalent among Group 1 women. There was a trend to higher basal 17OHP among Group 1 patients (mean +/- SEM; 1354+/-323 vs 714+/-129 ng/dl, P< or =0.25). The lack of significant difference was perhaps due to the relatively few homozygotes for 2 mild mutations (24%). V281L was carried on approximately 48% of all alleles, and about 16% carried either P30L or P453S. Approximately 38% of alleles and 77% of patients carried a classic mutation. These data have important implications for genetic counseling. In summary, we describe differences in clinical, hormonal, and genetic characteristics among a multiethnic group of females with NCAH.
authors.affiliation: Department of Pediatrics, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA. speiser@nshs.edu
authors.forename: P W
authors.initials: PW
authors.lastname: Speiser
authors.forename: E S
authors.initials: ES
authors.lastname: Knochenhauer
authors.forename: D
authors.initials: D
authors.lastname: Dewailly
authors.forename: F
authors.initials: F
authors.lastname: Fruzzetti
authors.forename: J A
authors.initials: JA
authors.lastname: Marcondes
authors.forename: R
authors.initials: R
authors.lastname: Azziz
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000152:Acne Vulgaris / Q000150:complications; D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D015992:Body Mass Index; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006628:Hirsutism / Q000150:complications; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009839:Oligomenorrhea / Q000150:complications; D010641:Phenotype; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D019326:17-alpha-Hydroxyprogesterone; D013255:Steroid 21-Hydroxylase