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Hormones

, Volume 15, Issue 2, pp 235–242 | Cite as

Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation

  • Christos Shammas
  • Stefania Byrou
  • Marie M. Phelan
  • Meropi Toumba
  • Charilaos Stylianou
  • Nicos Skordis
  • Vassos Neocleous
  • Leonidas A. Phylactou
Research paper

Abstract

OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an endocrine autosomal recessive disorder with various symptoms of diverse severity. Mild hyperandrogenemia is the most common clinical feature in non-classic CAH patients and 95% of the cases are identified by mutations in the CYP21A2 gene. In the present study, the second most common cause for non-classic CAH (NC-CAH), 11β-hydroxylase deficiency due to mutations in the CYP11B1 gene, is investigated. DESIGN: Screening of the CYP21A2 and CYP11B1 genes by direct sequencing was carried out for the detection of possible genetic defects in patients with suspected CAH. RESULTS: It was observed that CYP11B1 variants co-exist only in rare cases along with mutations in CYP21A2 in patients clinically diagnosed with CAH. A total of 23 NC-CAH female patients out of 75 were identified with only one mutation in the CYP21A2 gene. The novel CYP11B1 gene mutation, p.Val484Asp, was identified in a patient with CAH in the heterozygous state. The structural characterization of the novel p.Val484Asp was found to likely cause distortion of the surrounding beta sheet and indirect destabilization of the cavity that occurs on the opposite face of the structural elements, leading to partial impairment of the enzymatic activity. CONCLUSIONS: CYP21A2 gene mutations are the most frequent genetic defects in cases of NC-CAH even when these patients are in the heterozygous state. These mutations have a diverse phenotype giving rise to a variable extent of Cortisol synthesis impairment; it is also clear that CYP11B1 mutants are a rare type of defects causing CAH.

Key words

CYP11B1 Hyperandrogenemia Non-classic CAH PCOS Premature adrenarche 

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Copyright information

© Hellenic Endocrine Society 2016

Authors and Affiliations

  • Christos Shammas
    • 1
    • 5
  • Stefania Byrou
    • 1
    • 5
  • Marie M. Phelan
    • 2
    • 5
  • Meropi Toumba
    • 3
    • 5
  • Charilaos Stylianou
    • 4
    • 5
  • Nicos Skordis
    • 1
    • 5
  • Vassos Neocleous
    • 1
    • 5
  • Leonidas A. Phylactou
    • 1
    • 5
  1. 1.Department of Molecular Genetics, Function & TherapyThe Cyprus Institute of Neurology & GeneticsNicosiaCyprus
  2. 2.NMR Centre for Structural Biology, Institute of Integrative BiologyUniversity of LiverpoolLiverpoolUK
  3. 3.Division of PediatricsIasis HospitalPafosCyprus
  4. 4.Pediatric EndocrinologyPafos General HospitalPafosCyprus
  5. 5.St George’s, University of London Medical School at the University of NicosiaNicosiaCyprus

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