High carrier frequency of 21-hydroxylase deficiency in Cyprus

Authors

  • AAP Phedonos,

    1. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
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  • C Shammas,

    1. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
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  • N Skordis,

    1. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
    2. Paediatric Endocrine Unit, Makarios III Hospital, Nicosia, Cyprus
    3. St George's University of London Medical School at the University of Nicosia, Nicosia, Cyprus
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  • TC Kyriakides,

    1. Department of Epidemiology & Public Health, Yale University, New Haven, CT, USA
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  • V Neocleous,

    1. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
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  • LA Phylactou

    Corresponding author
    1. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
    • Corresponding author: Leonidas A Phylactou, PhD, Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus.

      Tel.: +35722358600;

      Fax: +35722392817;

      e-mail: laphylac@cing.ac.cy [P.O. Box 23462]

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  • The authors declare no conflict of interest.

Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder caused by mutations in the CYP21A2 gene. The carrier frequency of CYP21A2 mutations has been estimated to be 1:25 to 1:10 on the basis of newborn screening. The main objective of this study was to determine the carrier frequency in the Cypriot population of mutations in the CYP21A2 gene. Three hundred unrelated subjects (150 males and 150 females) from the general population of Cyprus were screened for mutations in the CYP21A2 gene and its promoter. The CYP21A2 genotype analysis identified six different mutants and revealed a carrier frequency of 9.83% with the mild p.Val281Leu being the most frequent (4.3%), followed by p.Qln318stop (2.5%), p.Pro453Ser (1.33%), p.Val304Met (0.83%), p.Pro482Ser (0.67%) and p.Met283Val (0.17%). The notable high CYP21A2 carrier frequency of the Cypriot population is one of the highest reported so far by genotype analysis. Knowledge of the mutational spectrum of CYP21A2 will enable to optimize mutation detection strategy for genetic diagnosis of 21-OHD not only in Cyprus, but also the greater Mediterranean region.

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