Linking the degree of virilization in females with congenital adrenal hyperplasia to genotype

Semyon Gurgov, Kerlly J. Bernabé, John Stites, Christopher M Cunniff, Karen Lin-Su, Diane Felsen, Maria I. New, Dix P. Poppas

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations. One hundred fifty-eight patients were sorted into groups by expected enzyme activity (percent of normal activity) of the less severely affected allele: (A) null, 0%; (B) I2G, 1%; (C) I172N, 2%; and (D) V281L, >2%. We observed an inverse relationship between virilization and residual enzyme activity (P < 0.001). Subjects in group A or B had a significantly higher likelihood (unadjusted odds ratio: 16; P < 0.001) of developing severe virilization compared with those in group C. Surprisingly, 24% of group D patients, whose mutation is usually associated with nonclassical (NC) CAH, had severe virilization. Among subjects with the NC P30L mutation, 66% expressed unexpected virilization. Virilization, usually leading to extensive reconstructive surgery, is highly likely in patients with null or I2G mutations; however, NC mutations (P30L/V281L) may also lead to unexpected virilization. These findings have implications for prenatal counseling and highlight the need for additional investigations into other factors that influence virilization in CAH.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - 2017


  • Congenital adrenal hyperplasia
  • Genetic mutation
  • Genital atypia
  • P30L mutation
  • Virilization

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


Dive into the research topics of 'Linking the degree of virilization in females with congenital adrenal hyperplasia to genotype'. Together they form a unique fingerprint.

Cite this