title: Point mutations in the promoter region of the CYBB gene leading to mild chronic granulomatous disease.
abstract: Chronic granulomatous disease (CGD) is a clinical syndrome of recurrent bacterial and fungal infections caused by a rare disorder of phagocytic cells. In CGD, the phagocytes are unable to generate oxygen radicals after stimulation of these cells, due to a defect in the NADPH oxidase system. This NADPH oxidase is a multicomponent enzyme of at least four subunits, of which the beta-subunit of cytochrome b558, gp91-phox, is encoded by an X-linked gene (called CYBB). We report here five patients from two families; in each family we found a different mutation in the promoter region of CYBB. Both mutations prevented the expression of gp91-phox in the patients' neutrophils and thus caused inability of these cells to generate oxygen radicals. However, the mutations left the gp91-phox expression and the function of the NADPH oxidase in the patients' eosinophils intact. The relatively mild course of the CGD in these patients can probably be attributed to the fact that the eosinophils have retained their oxidative capacity. Furthermore, our results indicate that neutrophils and eosinophils differ in their regulation of gp91-phox expression.
authors: Emma Children's Hospital and Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors: R S
authors: RS
authors: Weening
authors: M
authors: M
authors: De Boer
authors: T W
authors: TW
authors: Kuijpers
authors: V M
authors: VM
authors: Neefjes
authors: W W
authors: WW
authors: Hack
authors: D
authors: D
authors: Roos
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D002675:Child, Preschool; D003573:Cytochrome b Group / Q000235:genetics* / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010375:Pedigree; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012235:Rhodamines / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D060245:Tetraspanin 29; D015054:Zymosan / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; C554869:CD9 protein, human; D003573:Cytochrome b Group; D008562:Membrane Glycoproteins; D012235:Rhodamines; D060245:Tetraspanin 29; C058319:dihydrorhodamine 123; D015054:Zymosan; C036888:cytochrome b558; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate