Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population.

BACKGROUND: Congenital adrenal hyperplasia (CAH) due to autosomal recessive 21-hydroxylase deficiency (21-OHD) is caused by defects in the CYP21 (CYP21A2) gene. Several mutations have been identified in the CYP21 (CYP21A2) gene of patients with 21-OHD. We aimed at determining the frequency of these mutations among a group of Egyptian patients and studying the genotype-phenotype correlation. METHODS: Forty-seven patients with CAH due to 21-OHD from 42 different families diagnosed by clinical and hormonal evaluation and classified accordingly into salt wasting (SW) and simple virilizing (SV) phenotypes were enrolled. Their ages ranged between 1.78 and 18.99 years. Molecular analysis of the CYP21 (CYP21A2) gene was performed for the detection of eleven common mutations: P30L, I2 splice (I2 G), Del 8 bp E3 (G110del8nt), I172N, cluster E6 (I236N, V237E, M239K), V281L, L307 frameshift (F306 + T), Q318X, R356W, P453S, R483P by polymerase chain reaction (PCR) and reverse hybridization. RESULTS: Disease-causing mutations were identified in 47 patients, 55.31% of them were compound heterozygous. The most frequent mutations were I2 splice (25.43%), followed by cluster E6 (16.66%) and P30L (15.78%). Two point mutations (P453S, R483P) were not identified in any patient. In the SW patients, genotypes were more compatible with their phenotypes. CONCLUSION: Molecular characterization should be considered along with clinical and biochemical diagnosis of CAH since it could confirm the diagnosis, outline the treatment strategy and morbidity, and ensure proper genetic counseling.