Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt

Mona Essawi 1 , Inas Mazen 2 , Lubna Fawaz 3 , Heba Hassanhttp://orcid.org/https://orcid.org/0000-0002-9567-0896 1 , Nagham ElBagoury 1 , Michael Peter 4 , Khadiga Gaafar 5 , Mahmoud Amer 5 , Wajeet Nabil 5 , Gisela Hohmann 4 , Hala Soliman 1 ,  and Wolfgang Sippell 4
  • 1 Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt
  • 2 Clinical Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt
  • 3 Diabetes, Endocrinology & Metabolic Pediatric Unit, Cairo University, Cairo, Egypt
  • 4 Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian–Albrechts-Universität zu Kiel, Kiel, Germany
  • 5 Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt
Mona Essawi
  • Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt
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, Inas Mazen
  • Clinical Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt
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, Lubna Fawaz, Heba HassanORCID iD: https://orcid.org/0000-0002-9567-0896, Nagham ElBagoury
  • Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt
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, Michael Peter
  • Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian–Albrechts-Universität zu Kiel, Kiel, Germany
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, Khadiga Gaafar, Mahmoud Amer, Wajeet Nabil, Gisela Hohmann
  • Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian–Albrechts-Universität zu Kiel, Kiel, Germany
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, Hala Soliman
  • Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt
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and Wolfgang Sippell
  • Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian–Albrechts-Universität zu Kiel, Kiel, Germany
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Abstract

Objectives

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder caused by defects in the CYP21A2 gene. We aimed to determine the prevalence of the most commonly reported mutations among 21-OHD Egyptian patients and correlate genotype with phenotype.

Methods

Molecular analysis of the CYP21A2 gene was performed for the detection of the six most common point mutations (p.P30L, p.I172N, p.V281L, p.Q318X, the splice site mutation Int2 [IVS2–13A/C>G], and the cluster of three mutations [p.I236N, p.V237E, and p.M239K] designed as CL6). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was performed on 47 unrelated Egyptian 21α-OH deficiency patients and their available parents to detect the presence of the six most common point mutations.

Results

Screening for the six most common point mutations in CYP21A2 gene, revealed mutations in 87.2% (82/94) of the studied alleles corresponding to 47 Egyptian patients. The most common mutation among the studied cases was IVS2-13C/A>G that was found to be presented in a frequency of 46.8% (44/94). The genotype/phenotype correlations related to null, A, and B groups were with PPV of 100, 55.5, and 83.3%, respectively.

Conclusions

The described method diagnosed CAH in 80.8% of the studied patients. Good correlation between genotype and phenotype in salt wasting and simple virilizing forms is determined, whereas little concordance is seen in nonclassical one. Furthermore, studying the carrier frequency of 21-OHD among the normal population is of great importance.

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The Journal of Pediatric Endocrinology and Metabolism (JPEM) is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups, and publishes the results of clinical investigations in pediatric endocrinology and basic research. JPEM publishes Review Articles, Original Research, Case Reports, Short Communications and Letters to the Editor.

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