comparative analysis of CYP21A2 gene mutations among different classes of CAH in Iranian patients

Introduction: Cortisol and aldosterone biosynthesis dysfunction is mainly due to 21-hydroxylase deficiency which leads to a rare autosomal recessive disorder, known as Congenital Adrenal Hyperplasia. Two main types of CAH included severe or classical and mild late onset or non‐classical. CYP21A2 gene is responsible for at least 95% of all CAH and other related genes are involved including CYP11B1, HSD3B2, STAR and etc. In this study CYP21A2 gene mutations were analyzed and correlated to the phenotype based on genotypes and compared to clinical characteristicsMaterials & Methods: DNA extraction for ninety eight subjects, clinically diagnosed with CAH, was performed. All coding and noncoding regains of CYP21A2 gene were amplified and then sequenced. The sequenced fragments were analyzed and pathogenic mutations were confirmed by segregation analysis.Results: Mutation in CYP21A2 gene was detected in 45% of cases, 53% of individuals showed no change and the rest had mutations in other genes. Frequency of Classic and Non-classic forms of CAH was: (36% SW and 30% SV) and 30% (NC-CAH), respectively. Furthermore, we detected new substitution in one cases with unknown enzyme activity and also, a homozygous mutation was detected in CYP11B1 gene in two patients Conclusion & discussion: Congenital Adrenal Hyperplasia is frequent in Iranian population due to consanguineous marriages. Prevalence of classic type has been estimated more than non-classic form in our studied population, therefore genetic testing helps to confirm the clinical diagnosis and prenatal diagnosis in affected families. On the other hand, we found that other responsible genes in cortisol synthetize pathway could be of importance. Thus in cases with normal genotype of CYP21A2 gene, molecular analysis for other related genes can be effective

کلیدواژه ها:

CYP21A2 ، genetic testing ، NC-CAH ، simple virilizing (SV-CAH) and salt wasting (SW-CAH)