Identification of Cytochrome b‐245, beta‐chain gene mutations, and clinical presentations in Iranian patients with X‐linked chronic granulomatous disease. Issue 2 (23rd October 2020)

• Record Type: Journal Article
• Authors: Heydari, Atefeh; Abolnezhadian, Farhad; Sadeghi‐Shabestari, Mahnaz; Saberi, Alihossein; Shamsizadeh, Ahmad; Ghadiri, Ata A.; Ghandil, Pegah
• Is Part Of: Journal of clinical laboratory analysis. Volume 35:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-23
• Subjects: CYBB gene -- immunodeficiency -- mutation -- patients -- X‐linked chronic granulomatous disease (X‐CGD); Diagnosis, Laboratory -- Periodicals; Medical laboratory technology -- Periodicals; 616
• DOI: 10.1002/jcla.23637
• Languages: English
• ISSNs: 0887-8013

Abstract

Abstract: 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. Abstract : We studied four Iranian patients suspected to X‐linked chronic granulomatous disease and their families. One novel and three known mutations were detected. The clinical features of them have been presented. The pathogenic effect of the novel mutations was confirmed by bioinformatics analysis.