A novel missense mutation in the NADPH binding domain of CYBB abolishes the NADPH oxidase activity in a male patient with increased susceptibility to infections

التفاصيل البيبلوغرافية
العنوان: A novel missense mutation in the NADPH binding domain of CYBB abolishes the NADPH oxidase activity in a male patient with increased susceptibility to infections
المؤلفون: Hazir Rahman, Huma Asif, Taj Ali Khan, Mubashir Hussain, Hassan Naveed, Hamid Nawaz Tipu, Andrei Florea, Umar Nasir, Kalsoom Kalsoom, Muhammad Usman Amin, Asif Iqbal, Syed Omar Farooq
المصدر: Microbial Pathogenesis. 100:163-169
بيانات النشر: Elsevier BV, 2016.
سنة النشر: 2016
مصطلحات موضوعية: Male, 0301 basic medicine, Mutation, Missense, Granulomatous Disease, Chronic, medicine.disease_cause, Communicable Diseases, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Chronic granulomatous disease, Phagocytosis, medicine, Humans, Missense mutation, Genetic Predisposition to Disease, CYBB, Cells, Cultured, Respiratory Burst, Mutation, Membrane Glycoproteins, NADPH oxidase, biology, Macrophages, NADPH Oxidases, Sequence Analysis, DNA, Flow Cytometry, medicine.disease, biology.organism_classification, Molecular biology, Respiratory burst, 030104 developmental biology, Infectious Diseases, NADPH Oxidase 2, Immunology, biology.protein, NADPH binding, 030215 immunology
الوصف: Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the five structural genes (CYBB, CYBA, NCF1, NCF2, and NCF4) that typically results in a decrease in function or inability to generate a respiratory burst, leading to defective killing of pathogens, including fungi and intracellular bacteria. Mutations in CYBB, encoding the gp91phox (also known as NOX2) result in X-linked CGD account for approximately 65% of CGD cases. Here, we aimed the characterization of a novel missense mutation c.1226C > A/p.A409E in the CYBB gene in a patient with X-linked CGD. Relevant clinical data of a male patient whose family was positive for XCGD was reviewed. Oxidative burst and NADPH protein expression was evaluated by flow cytometry, while Genetic analysis was performed by Sanger sequencing. Monocyte-derived macrophages (MDMs) were evaluated for their capacity for phagocytosis and growth suppression of the intracellular Mycobacterium tuberculosis (M. tuberculosis). We thus report the absence of an oxidative burst in the phagocytes of the patient. Flow cytometry evaluation revealed a normal expression of NADPH oxidase components in neutrophils and genetic analysis proved the existence of a novel missense c.1226C > A mutation in the CYBB gene resulting in p.A409E. Further, we have showed that the patient's MDMs were unhindered in their ability to take up mycobacteria normally. Instead, the MDMs failed to control the intracellular proliferation of M. tuberculosis, a phenotype that improved in the presence of recombinant human interferon-gamma (rhIFN-γ). This work expands the genetic spectrum of X-linked CGD and demonstrates improvement in macrophage function in X91+CGD patient by rhIFN-γ.
تدمد: 0882-4010
DOI: 10.1016/j.micpath.2016.09.020
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1c68b1b2ce9f96fc9e821ecf6e19030
https://doi.org/10.1016/j.micpath.2016.09.020
Rights: CLOSED
رقم الانضمام: edsair.doi.dedup.....c1c68b1b2ce9f96fc9e821ecf6e19030
قاعدة البيانات: OpenAIRE
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