Search our Database of Scientific Publications and Authors

I’m looking for a

    Details and Download Full Text PDF:
    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.

    Microb Pathog 2016 Nov 23;100:163-169. Epub 2016 Sep 23.
    The Department of Chemistry, University of Oxford, Oxford, United Kingdom.
    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 X91CGD patient by rhIFN-γ.
    PDF Download - Full Text Link
    ( Please be advised that this article is hosted on an external website not affiliated with PubFacts.com)
    Source Status
    http://dx.doi.org/10.1016/j.micpath.2016.09.020DOI ListingPossible

    Similar Publications

    Monocyte/macrophage-specific NADPH oxidase contributes to antimicrobial host defense in X-CGD.
    J Clin Immunol 2015 Feb 10;35(2):158-67. Epub 2015 Feb 10.
    Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan,
    Background: Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. Various mutations in CYBB encoding the gp91(phox) subunit of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase impair the respiratory burst of all types of phagocytic cells and result in X-linked CGD (X-CGD).

    Purpose: We here sought to evaluate the underlying cause in an attenuated phenotype in an X-CGD patient. Read More
    Characterization of six novel mutations in the CYBB gene leading to different sub-types of X-linked chronic granulomatous disease.
    Hum Genet 2005 Jan 6;116(1-2):72-82. Epub 2004 Nov 6.
    Laboratoire d'Enzymologie, GREPI EA 2938 UJF, CHU 38043, Grenoble Cedex 9, France.
    Chronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and so cannot generate superoxide anions (O(2) (-)). The most common form is caused by mutations in CYBB encoding gp91 phox, the heavy chain of flavocytochrome b(558) (XCGD). We investigated 11 male patients and their families suspected of suffering from X-linked CGD. Read More
    Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients.
    J Allergy Clin Immunol 2013 Nov 31;132(5):1156-1163.e5. Epub 2013 Jul 31.
    Immunology Department and GenKök Laboratory of Immunology, Faculty of Medicine, University of Erciyes, Kayseri, Turkey. Electronic address:
    Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22(phox), p47(phox), p67(phox), and p40(phox) of the leukocyte nicotinamide dinucleotide phosphate reduced (NADPH) oxidase leads to autosomal recessive (AR) CGD. A mutation in the CYBB gene encoding gp91(phox) leads to X-linked recessive CGD. Read More