title: Clinical evaluation of interferon-gamma treatment to chronic granulomatous disease patients with splice site mutations.
abstract: IFN-gamma dependent increase of superoxide production by neutrophils was observed in three patients with Chronic Granulomatous disease from one family. The patients have the gp91-phox defect due to a splicing abnormality derived from a silent mutation adjacent to the third intron of CYBB gene. Apparent differences of splicing pattern of CYBB gene transcripts in patients' neutrophils were detected between 1 and 25 days after administration of IFN-gamma. Furthermore, the transcript containing all missing exons could be detected in all specimens after the treatment. The changes of splicing pattern in the transcripts and prolonged effect on superoxide generating ability of patients' neutrophils indicate that IFN-gamma induced an ability to correct abnormal splicing of CYBB gene transcripts in progenitor cells at least in part.
authors.affiliation: Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan. h-nunoi@fc.miyazaki-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nunoi
authors.forename: Fuminari
authors.initials: F
authors.lastname: Ishibashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mizukami
authors.forename: Fumio
authors.initials: F
authors.lastname: Hidaka
mesh_terms: D000293:Adolescent; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006105:Granulomatous Disease, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D012326:RNA Splicing / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D013481:Superoxides; D007371:Interferon-gamma; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases