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Horm Metab Res 2019; 51(09): 586-594
DOI: 10.1055/a-0957-3297
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

The Spectrum of Genetic Defects in Congenital Adrenal Hyperplasia in the Population of Cyprus: A Retrospective Analysis

Vassos Neocleous
1   Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
2   Cyprus School of Molecular Medicine, Nicosia, Cyprus
,
Pavlos Fanis
1   Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
2   Cyprus School of Molecular Medicine, Nicosia, Cyprus
,
Meropi Toumba
1   Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
3   Pediatric Endocrine Clinic, IASIS Hospital, Paphos, Cyprus
,
Charilaos Stylianou
4   Division of Pediatric Endocrinology, Makarios III Hospital, Nicosia, Cyprus
,
Michalis Picolos
5   Alithias Endocrinology Center, Nicosia, Cyprus
,
Elena Andreou
6   Dasoupolis Endocrinology Center, Andrea Dimitriou Street Dasoupolis, Nicosia, Cyprus
,
Andreas Kyriakou
7   Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, UK
,
Michalis Iasonides
8   Iliaktida Peadiatric & Adolescent Medical Centre, Limassol, Cyprus
,
Stella Nicolaou
4   Division of Pediatric Endocrinology, Makarios III Hospital, Nicosia, Cyprus
,
Tassos C. Kyriakides
9   Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, USA
,
George A. Tanteles
2   Cyprus School of Molecular Medicine, Nicosia, Cyprus
10   Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
,
Nicos Skordis
1   Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
11   Division of Pediatric Endocrinology, Paedi Center for Specialized Pediatrics, Nicosia, Cyprus
12   St George’s, University of London Medical School at the University of Nicosia, Nicosia, Cyprus
,
Leonidas A. Phylactou
1   Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
2   Cyprus School of Molecular Medicine, Nicosia, Cyprus
› Author Affiliations
Further Information

Publication History

received 18 March 2019

accepted 06 June 2019

Publication Date:
10 September 2019 (online)

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Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is caused by mutations in the CYP21A2 gene. The study refers to CAH patients of Greek-Cypriot ancestry between years 2007 and 2018. One hundred and twenty patients with various degrees of CAH were categorized and genotyped. The patients were categorized in 4 mutation groups based on their clinical and biochemical findings. The majority of patients (85.0%) belonged to the non-classic (NC)-CAH form and the disorder was more often diagnosed in females (71.7%). The most severe classic salt-wasting (SW) form was identified in 11 neonates (9.2%). Seven (5.8%) children were also identified with the simple virilizing (SV) form and a median presentation age of 5 years [interquartile range (IQR) 3.2–6.5]. In the 240 nonrelated alleles, the most frequent mutation was p.Val281Leu (60.0%) followed by c.655 A/C>G (IVS2–13A/C>G) (8.8%), p.Pro453Ser (5.8%), DelEx1–3 (4.6%), p.Val304Met (4.6%), and p.Gln318stop (4.2%). Other less frequent mutations including rare deletions were also identified. Following our recent report that the true carrier frequency of CYP21A2 in Greek-Cypriots is 1:10, this study reports that the CAH prevalence is predicted around 1.7 cases per 10 000 people. Therefore, the up-to-date 120 CAH patients identified by our group make only the 6.9% of the ones estimated (approximately 1750) to exist in the Greek Cypriot population. The compiled data from a coherent population such as the Greek-Cypriot could be valuable for the antenatal diagnosis, management and genetic counselling of the existing and prospect families with CAH.

Key words

congenital adrenal hyperplasia - CYP21A2 - 21-hyrdroxylase deficiency
 

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