Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt
Author:
Essawi Mona1, Mazen Inas2, Fawaz Lubna3, Hassan Heba1ORCID, ElBagoury Nagham1, Peter Michael4, Gaafar Khadiga5, Amer Mahmoud5, Nabil Wajeet5, Hohmann Gisela4, Soliman Hala1, Sippell Wolfgang4
Affiliation:
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
Abstract
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.
Funder
National Research Centre
Publisher
Walter de Gruyter GmbH
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism,Pediatrics, Perinatology and Child Health
Reference41 articles.
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