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Genetic defects of the CYP21A2 gene in girls with premature adrenarche

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Abstract

Objectives

To seek evidence on the prevalence of CYP21A2 genetic defects and consequences in girls with premature adrenarche (PA).

Methods

The study included 59 girls diagnosed with PA. Direct DNA sequencing and MLPA analysis were performed to identify mutations in CYP21A2 gene.

Results

Twelve girls were diagnosed with non-classic congenital adrenal hyperplasia (NC-CAH) based on stimulated 17-hydroxyprogesterone (17-OHP) levels and the presence of two mutations in CYP21A2, 19 were heterozygotes. The most frequent mutations detected were the mild p.Val281Leu and p.Pro453Ser. Higher levels of mean stimulated 17-OHP were found in the carriers of the p.Val281Leu mutation. The detection rate for two CYP21A2 mutations was higher in girls with PA than in adult females with hyperandrogenemia in our studied population. A notable increased allelic frequency for the known p.Asn493Ser polymorphism was observed in the pool of the 28 girls with PA in whom no mutation was identified.

Conclusions

In girls with PA, the frequency of the underlying CYP21A2 genetic defects is similar to that observed in other populations. The carrier status is likely a contributing factor in the genotype–phenotype correlation in NC-CAH. However, polymorphisms and other genes may be implicated in the clinical manifestation of the disease.

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Abbreviations

CAH:

Congenital adrenal hyperplasia

NC-CAH:

Non-classical congenital adrenal hyperplasia

17-OHP:

17-Hydroxyprogesterone

21-OHD:

21-Hydroxylase deficiency

ACTH:

Adrenocorticotropic hormone

PCOS:

Polycystic ovary syndrome

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Acknowledgments

The Project ΥΓΕΙΑ/ΔΥΓΕΙΑ/0609/(ΒΙΕ)/27 is co-financed by the European Development Fund and the Republic of Cyprus through the Research Promotion Foundation.

Conflict of interest

The authors declare that they do not have any conflicts of interest and no financial relationships that might have influenced the present work.

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683, Nicosia, Cyprus

    N. Skordis, C. Shammas, A. A. P. Phedonos, V. Neocleous & L. A. Phylactou

  2. Division of Pediatric Endocrinology, Paedi Center for Specialized Pediatrics, Nicosia, Cyprus

    N. Skordis & A. Kyriakou

  3. St George’s, University of London Medical School Programme at the University of Nicosia, Nicosia, Cyprus

    N. Skordis

  4. Developmental Endocrinology Research Group, Royal Hospital for Sick Children, University of Glasgow, Glasgow, UK

    A. Kyriakou

  5. Iasis Hospital, 8036, Paphos, Cyprus

    M. Toumba

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  1. N. Skordis
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Correspondence to L. A. Phylactou.

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Skordis, N., Shammas, C., Phedonos, A.A.P. et al. Genetic defects of the CYP21A2 gene in girls with premature adrenarche. J Endocrinol Invest 38, 535–539 (2015). https://doi.org/10.1007/s40618-014-0223-1

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  • DOI: https://doi.org/10.1007/s40618-014-0223-1

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