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

Affiliation

Heydari A(1)(2), Abolnezhadian F(3), Sadeghi-Shabestari M(4), Saberi A(2), Shamsizadeh A(5), Ghadiri AA(6), Ghandil P(1)(2)(7).
Author information:
(1)Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
(2)Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
(3)Department of Pediatrics, Abuzar Children's Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
(4)Immunology research center of Tabriz-TB and lung research center of Tabriz-children hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
(5)Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
(6)Department of Immunology, Cellular and Molecular Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
(7)Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

BACKGROUND: X-linked chronic granulomatous disease (X-CGD) is an immunodeficiency disorder caused by defects in the gp91phox 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.