Genetic Investigation of CYBB Gene in Iranian Patients with X-CGD

چکیده مقاله

Chronic Granulomatous Disease is an inherited phagocytic disorder causing reduced nicotinamide dinucleotide phosphate (NADPH) oxidase complex activity, results in defective superoxide generation and intracellular killing. CGD patients present recurrent life-threatening bacterial and fungal infections; chronic granulomas and poor wound healing. CGD may be inherited in an X-linked (X) or autosomal recessive (AR) manner. However, X-CGD is far more common, accounting for about 70% of all CGD cases. X-CGD is because of mutation in CYBB gene (GenBank Accession Nos.AF469757-Af469769). This gene is located on chromosome Xp21.1, spans 30 kb and contains 13 exons. Over 300 CYBB mutations have been registered in an internationally maintained X-CGD database (X-CGD base). Most mutations are distributed throughout the 13 exons or at exon/intron boundaries and almost 200 of these mutations are unique. In this study, we analyzed 24 patients with clinically diagnosed CGD. Mutation in CYBB gene was detected using SSCP analysis (single-strand conformation polymorphism) followed by sequencing. During screening for mutations in the CYBB gene we observed 880 C T in exon 8. This mutation results in 290 Arg Stop . We also observed a change (-270 C A) in the promoter region, which needs further investigation. We would like to pursue this study by analyzing more X-CGD patients to find out the CYBB mutation spectrum in Iranian patients. Characterization of mutant exons is very important for detection of carriers, prenatal al diagnosis and final diagnosis of disease.