Congenital adrenal hyperplasia (CAH) is a defect of cortisol biosynthesis. The most common cause of CAH is 21-hydroxylase deficiency (21-OHD) caused by CYP21A2 gene mutations. 21-hydroxylase activity is correlated with different clinical presentations such as salt-wasting (SW), simple-virilizing (SV), and non-classical (NC) CAH. We aimed to determine the CYP21A2 gene mutations and evaluate the genotype-phenotype correlation in 21-OHD patients to value the impact of these mutations for clinical management.
CYP21A2 gene mutation analysis with respect to common mutations P30L, IVS2, I172N, cluster E6, V281L,Q318X,R356W, Del 8-bp E3, P453S, R483P, L307 frameshift, large deletions, and conversions was performed by different methods namely RFLP, MLPA and reverse-hybridization, in 42 CAH patients from 38 families.
The mean age of the patients was 2.5 years. Ambiguous genitalia (45.2%) and vomiting/weight loss (23.8%) were the most common clinical presentations. 50% of the patients were in SW, 33.3% in SV, and 16.6% in NC forms. Mutations were found in 94% of 84 alleles. 88.1% of the patients had more than one mutations. 59.5% of the patients presented with homozygous genotype, whereas 28.6% were compound heterozygous. The most common mutations were IVS2 (22.6%), I172N (22.6%), Q318X (15.4%), and large deletions (14.2%). Q318X, large deletions, R356W, and cluster E6 mutations were more correlated to SW, I172N was more common in SV, and V281L was seen more frequently in NC.
Genotypes were well-correlated with phenotypes within clinical subtypes in most of the patients. The most common mutations were IVS2 and I172N in our study group. We believe that these data as well as others in the literature will serve for better genetic counseling in daily practice of CAH.