High frequency of splice site mutation in 21-hydroxylase deficiency children

Steroid 21-hydroxylase deficiency (21-OHD) is the common type of congenital adrenal hyperplasia (CAH) caused by defects in the CYP21A2 gene, as an autosomal recessive disease, genetic analysis has a prominent role in its diagnosis. Our objectives were to determine the prevalence of common mutations in a group of Egyptian patients with 21-OHD and their families using rapid methods, and also to detect the rate of deletion, duplication and conversions in CYP21A2 gene.

Rapid detection methods were used: allele-specific PCR for c.293-13A>G (g.659A>G), c.518T>A (p.I172N) variants and c.332_339del (8-bp deletion in exon 3), and real-time, quantitative PCR assay was used to detect deletion in the CYP21A2 gene. 29 Egyptian patients, 38 family members, and 20 healthy controls were all included in the study.

The frequency of c.293-13A>G splice mutation was reported in 96.6 % cases, G allele had 2.5-folds higher risk to develop CAH than other alleles. The c.518T>A mutation was reported in 69 % cases, children carrying the mutant allele were 2.1 times more risk. The most frequent combined mutations detected were c.293-13A/C>G/c.518T>A in 58.6 % cases.

The genetic analysis of the splice site mutation c.293-13A>G and c.518T>A variant can be used as good biomarkers for early detection of cases and carriers in 21-OHD CAH Egyptian children, since the methods used have rapid turnaround time.