Identification of Cytochrome b-245, beta-chain gene mutations, and clinical presentations in Iranian patients with X-linked chronic granulomatous disease

Background X-linked chronic granulomatous disease (X-CGD) is an immunodeficiency disorder caused by defects in the gp91(phox) subunit that leads to life-threatening infections. We aimed to identify CYBB gene mutations and study clinical phenotypes in Iranian patients with probable X-CGD. Methods We studied four unrelated Iranian patients with probable X-CGD and their families recruited in several years. We isolated genomic DNA from whole blood and performed Sanger sequencing in the CYBB gene's coding and flanking regions. We also performed pathogenicity predictions using in silico tools. Results We detected four different mutations, including a novel insertion mutation in exon 5 (p.Ile117AsnfsX6), in the patient. Bioinformatics analysis confirmed the pathogenic effect of this mutation. We predicted protein modeling and demonstrated lost functional domains. The patient with the insertion mutation presented pneumonia and acute sinusitis during his life. We also detected three other known nonsense mutations (p.Arg157Ter, p.Arg226Ter, and p.Trp424Ter) in the CYBB gene. The patient with p.Arg157Ter developed lymphadenitis and pneumonia. Moreover, the patient with inflammatory bowel disease showed p.Arg226Ter and the patient with tuberculosis presented p.Trp424Ter. We detected different clinical features in the patients compared to other Iranian patients with the same mutations. Conclusion Our results expand the genetic database of patients with X-CGD from Iran and make it much easier and faster to identify patients with X-CGD. Our results also help to detect carriers and enable prenatal diagnosis in high-risk families as a cost-effective strategy.

Automated summary

This study identified CYBB gene mutations in four Iranian patients with X-linked chronic granulomatous disease (X-CGD), including a novel insertion mutation. The patients exhibited different clinical features compared to other Iranian patients with the same mutations. The findings expand the genetic database of X-CGD patients from Iran and provide valuable information for carrier detection and prenatal diagnosis in high-risk families.