The molecular basis and genotype–phenotype correlations of congenital adrenal hyperplasia (CAH) in Anatolian population

  • Ayca Dundar
  • Ruslan Bayramov
  • Muge G. Onal
  • Mustafa Akkus
  • Muhammet E. Dogan
  • Sercan Kenanoglu
  • Meltem Cerrah Gunes
  • Ulviye Kazimli
  • Mehmet N. Ozbek
  • Oya Ercan
  • Ruken Yildirim
  • Gamze Celmeli
  • Mesut Parlak
  • Ismail Dundar
  • Nihal Hatipoglu
  • Kursad Unluhizarci
  • Hilal Akalin
  • Yusuf Ozkul
  • Cetin Saatci
  • Munis DundarEmail author
Original Article


Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants’ frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.


Congenital adrenal hyperplasia CYP21A2 CYP11B1 HSD3B2 Variants 



The authors would like to thank all study participants and all centers who acknowledge this work for contributing their time and supply of patients.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.

Supplementary material

11033_2019_4809_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 18 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Ayca Dundar
    • 1
    • 2
  • Ruslan Bayramov
    • 3
  • Muge G. Onal
    • 1
    • 4
  • Mustafa Akkus
    • 1
    • 4
  • Muhammet E. Dogan
    • 1
  • Sercan Kenanoglu
    • 1
  • Meltem Cerrah Gunes
    • 1
  • Ulviye Kazimli
    • 1
  • Mehmet N. Ozbek
    • 5
  • Oya Ercan
    • 6
  • Ruken Yildirim
    • 7
  • Gamze Celmeli
    • 8
  • Mesut Parlak
    • 9
  • Ismail Dundar
    • 10
  • Nihal Hatipoglu
    • 11
  • Kursad Unluhizarci
    • 12
  • Hilal Akalin
    • 1
  • Yusuf Ozkul
    • 1
    • 4
  • Cetin Saatci
    • 1
  • Munis Dundar
    • 1
    Email author
  1. 1.Department of Medical GeneticsErciyes UniversityKayseriTurkey
  2. 2.Department of RadiologyMayo ClinicRochesterUSA
  3. 3.Department of Medical GeneticsDETA-Gen Genetic Diagnosis CenterKayseriTurkey
  4. 4.Betul-Ziya Eren Genome and Stem Cell CenterErciyes UniversityKayseriTurkey
  5. 5.Department of Pediatric EndocrinologyDiyarbakir SBU Gazi Yasargil Education and Research HospitalDiyarbakirTurkey
  6. 6.Division of Pediatric EndocrinologyIstanbul University-CerrahpasaIstanbulTurkey
  7. 7.Department of Pediatric EndocrinologyDiyarbakir Children HospitalDiyarbakirTurkey
  8. 8.Department of Pediatric EndocrinologyAntalya Education and Research HospitalAntalyaTurkey
  9. 9.Department of Pediatric EndocrinologyAkdeniz UniversityAntalyaTurkey
  10. 10.Department of Pediatric EndocrinologyMalatya Education and Research HospitalMalatyaTurkey
  11. 11.Department of Pediatric EndocrinologyErciyes UniversityKayseriTurkey
  12. 12.Department of EndocrinologyErciyes UniversityKayseriTurkey

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