الفهرس 
Molecular analysis of CYP21A2 mutations in Egyptian patients with 21-hydroxylase deficiency
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Abstract
Background: Congenital adrenal hyperplasia (CAH) due 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. It is caused by defects in the CYP21A2 gene. Aim of the work: The aim of the present study was to determine the frequency of common CYP21A2 gene mutations and to evaluate genotype-phenotype correlations in Egyptian 21-OHD patients. Also to perform further sequencing for cases without any common mutations or with one heterozygote mutation. Methods: Molecular analysis of the CYP21A2 gene was performed using Strip Hybridization assay for the detection of the eleven common mutations (p.P30L, I2 Splice C/A>G, 8-bp-deletion, p.I172N, exon 6 mutation cluster, p.V281L, p.L307FS, p.Q318X, p.R356W, p.P453S and p.R483P) and Real-time PCR for gene dosage analysis in 100 patients with 21-OHD. Sequencing was done for cases without any mutation or with one heterozygous mutation. Results: Disease-causing mutations were identified in 182 out of 200 alleles (91%) of the patients. The most common mutation was I2 Splice C/A{u02C3}G (42.5%), while the second common was p.Q318X (20.5%). In 18 alleles (9%), no mutations were found. The overall concordance between genotype and phenotype was 70%. Genotype predicted phenotype in 91%, 66.7% and 12.5% of patients with salt-wasting, simple virilizing and nonclassical mutations, respectively. Further sequencing revealed one frameshift mutation (p.Leu10Profs) and two variants (p.Gly376=, p.Leu411Arg) that have not been described before. Conclusions: Based on these results, we propose a modified screening strategy to facilitate molecular testing of CAH patients in Egyptian population as this provides useful information in terms of prediction of disease severity, genetic and prenatal counseling