Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia

Carla Giordano, Francesca Di Gaudio, Marcello Niceta, Valentina Guarnotta, Marcello Niceta, Piernicola Garofalo, Serena Marchese, Marianna Bono, Carmelo Fabiano, Marianna Bono

Research output: Contribution to journalArticle

Abstract

Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carriers of CAH (33), respectively were selected. Forty-four females age-matched healthy controls were also enrolled and genotyped for CYP21A2. Clinical, hormonal and genetic data were collected. CYP21A2 monoallelic mutations, defining the heterozygous carriers state, were identified in subjects with clinical features including hirsutism, oligomenorrhoea, overweight and a PCO-like phenotype, particularly occurring in the age of adolescence. Consistently, levels of 17OHP and cortisol were found to be significantly different from NC-CAH. Overall, some clinical and laboratory findings including oligomenorrhea and 17OHP/cortisol ratio were observed as independent markers associated with carriers of CAH. Here we report a high prevalence of late-onset signs of polycystic ovary syndrome (PCOS) and hyperandrogenism in heterozygous carriers. The 17OHP/cortisol ratio may be a predictive tool to identify the carriers of CAH, even though specific cut-off values have not yet been identified.
Original languageEnglish
Pages (from-to)-00
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume198
Publication statusPublished - 2020

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Congenital Adrenal Hyperplasia
Heterozygote
Oligomenorrhea
Hyperandrogenism
Hydrocortisone
Phenotype
Carrier State
Hirsutism
Mutation
Inborn Genetic Diseases
Polycystic Ovary Syndrome
Genotype

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia. / Giordano, Carla; Di Gaudio, Francesca; Niceta, Marcello; Guarnotta, Valentina; Niceta, Marcello; Garofalo, Piernicola; Marchese, Serena; Bono, Marianna; Fabiano, Carmelo; Bono, Marianna.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 198, 2020, p. -00.

Research output: Contribution to journalArticle

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AU - Di Gaudio, Francesca

AU - Niceta, Marcello

AU - Guarnotta, Valentina

AU - Niceta, Marcello

AU - Garofalo, Piernicola

AU - Marchese, Serena

AU - Bono, Marianna

AU - Fabiano, Carmelo

AU - Bono, Marianna

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