title: A 40-base-pair duplication in the gp91-phox gene leading to X-linked chronic granulomatous disease.
abstract: Chronic granulomatous disease (CGD) is characterized by the inability of the patients' phagocytic leukocytes to generate superoxide. Therefore, these cells fail to kill certain bacteria and fungi. As a result, patients with CGD suffer from recurrent, life-threatening infections with these micro-organisms. Superoxide is produced by NADPH oxidase, a multicomponent enzyme exclusively present in phagocytic leukocytes. The most common form of CGD is X-linked, originating from a deficiency of the high-molecular-weight subunit of cytochrome b558 (gp91-phox). Here we describe a patient suffering from X-linked CGD due to a 40-base-pair duplication in exon 7 of the CYBB gene coding for gp91-phox, predicting a frameshift, substitution of 22 amino acids and a premature stop codon at amino-acid position 253. The mother as well as the grandmother of this patient were proven to be heterozygous for this mutation; the father and sister were normal. However, the great-grandmother proved to have normal oxidative functions, suggesting that the mutation occurred three generations ago. This is the first description of a nucleotide duplication leading to CGD.
authors.affiliation: Center for BioTechnology, Karolinska Institute, NOVUM, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Rabbani
authors.forename: M
authors.initials: M
authors.lastname: de Boer
authors.forename: A
authors.initials: A
authors.lastname: Ahlin
authors.forename: U
authors.initials: U
authors.lastname: Sundin
authors.forename: G
authors.initials: G
authors.lastname: Elinder
authors.forename: L
authors.initials: L
authors.lastname: Hammarström
authors.forename: J
authors.initials: J
authors.lastname: Palmblad
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Roos
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D003573:Cytochrome b Group / Q000235:genetics*; D005091:Exons; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000235:genetics*; D006801:Humans; D007223:Infant; D007438:Introns; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D019255:NADPH Oxidases; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000097:blood / Q000302:isolation & purification; D015183:Restriction Mapping; D014960:X Chromosome
chemical_list: D003573:Cytochrome b Group; D046911:Macromolecular Substances; D012313:RNA; C036888:cytochrome b558; D019255:NADPH Oxidases