title: A novel mutation in the CYBB gene resulting in an unexpected pattern of exon skipping and chronic granulomatous disease.
abstract: Chronic granulomatous disease is a rare inherited disorder caused by non-existent or severely decreased phagocyte superoxide production that results in a severe defect in host defense and consequent predisposition to microbial infection. The enzyme responsible for superoxide production, NADPH oxidase, involves at least five components. An absence of, or a defect in, any one of four of these proteins (p47(phox), p67(phox), p22(phox) and gp91(phox)) gives rise to the known types of chronic granulomatous disease. The most common form of inheritance is X-linked and is due to mutations in the CYBB gene that encodes gp91(phox), the large subunit of flavocytochrome b, the terminal electron donor of the oxidase. We have recently reported a large number of mutations in this gene revealing a broad range of defects, including large and small deletions, and frameshift, nonsense, missense, splice region and regulatory region mutations. Here we report a patient who has an unusual type of mutation that results in the generation of a 'pseudo-exon' in the gp91(phox) mRNA and an unexpected pattern of splicing.
authors.affiliation: Department of Molecular and Experimental Medicine, MEM-241, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: D
authors.initials: D
authors.lastname: Noack
authors.forename: P G
authors.initials: PG
authors.lastname: Heyworth
authors.forename: J T
authors.initials: JT
authors.lastname: Curnutte
authors.forename: J
authors.initials: J
authors.lastname: Rae
authors.forename: A R
authors.initials: AR
authors.lastname: Cross
mesh_terms: D001483:Base Sequence; D016384:Consensus Sequence; D004247:DNA / Q000097:blood / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D005091:Exons; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000737:chemistry
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D004247:DNA; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases