Open AccessIdentification of Cytochrome b‐245, beta‐chain gene mutations, and clinical presentations in Iranian patients with X‐linked chronic granulomatous disease
Author(s) -
Heydari Atefeh,
Abolnezhadian Farhad,
SadeghiShabestari Mahnaz,
Saberi Alihossein,
Shamsizadeh Ahmad,
Ghadiri Ata A.,
Ghandil Pegah
Publication year - 2021
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23637
Subject(s) - chronic granulomatous disease , sanger sequencing , primary immunodeficiency , exon , medicine , mutation , nonsense mutation , gene mutation , genetics , gene , biology , immunology , disease , missense mutation
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.