title: Characterization of 11 novel mutations in the X-linked chronic granulomatous disease (CYBB gene).
abstract: The most frequent form of chronic granulomatous disease (CGD) is caused by inactivation of the CYBB gene, which encodes the gp91-phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating bacterial and fungal infections. We investigated 16 unrelated male patients with suspected X-linked CGD and gp91-phox deficiency. A mutation was found in the CYBB gene of all 16 patients, and 11 of these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T, 919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X, R226X, Q231X, R290X, T307P, E462X, L505R gp-91phox). One patient had an in-frame deletion removing two amino acids (R54 and A55). Finally, insertions or duplications were found in four patients (from +1 to +31 bases). Overall, 12 (75%) of the mutations led to the production of a truncated protein. No clear correlation was found between clinical manifestations and genomic/biochemical alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat 18:163, 2001.
authors.affiliation: Service de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Gérard
authors.forename: J
authors.initials: J
authors.lastname: El Benna
authors.forename: F
authors.initials: F
authors.lastname: Alcain
authors.forename: M A
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
authors.forename: S
authors.initials: S
authors.lastname: Chollet-Martin
mesh_terms: D003573:Cytochrome b Group / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009504:Neutrophils / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D017382:Reactive Oxygen Species / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
chemical_list: D003573:Cytochrome b Group; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C036888:cytochrome b558; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases