title: An unusual intronic mutation in the CYBB gene giving rise to chronic granulomatous disease.
abstract: The most common, X-linked, form of chronic granulomatous disease (CGD) is caused by mutations in the CYBB gene located at Xp21.1. The product of this gene is the large subunit of flavocytochrome b558, gp91phox, which forms the catalytic core of the antimicrobial superoxide-generating enzyme, NADPH oxidase. In the overwhelming majority of cases, mutations are family-specific and occur in the exonic regions of the gene, or more rarely at the intron/exon borders. Alternatively, they are large (often multi-gene) deletions. In addition, four mutations have been found in the promoter region. In contrast, very few intronic mutations have been reported. Here we describe an intronic mutation that causes X-linked CGD. A single nucleotide substitution in the middle of intron V creates a novel 5' splice site and results in multiple abnormal mRNA products.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, 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: P E
authors.initials: PE
authors.lastname: Newburger
authors.forename: A R
authors.initials: AR
authors.lastname: Cross
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D005091:Exons; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000737:chemistry / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D008562:Membrane Glycoproteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases