A multicenter study of women with nonclassical congenital adrenal hyperplasia: Relationship between genotype and phenotype

Phyllis W. Speiser, Eric S. Knochenhauer, Didier Dewailly, Franca Fruzzetti, Jose A.M. Marcondes, Ricardo Azziz

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65 Scopus citations


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 ≤ 0.25). The lack of significant difference was perhaps due to the relatively few homozygotes for 2 mild mutations (24%). V281L was carried on ~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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number3
StatePublished - Jan 1 2000



  • Congenital adrenal hyperplasia
  • Genotype
  • Nonclassical
  • Phenotype
  • Steroid 21-monooxygenase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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