title: X-Linked chronic granulomatous disease: mutations in the CYBB gene encoding the gp91-phox component of respiratory-burst oxidase.
abstract: Chronic granulomatous disease (CGD) is a hereditary disorder of host defense due to absent or decreased activity of phagocyte NADPH oxidase. The X-linked form of the disease derives from defects in the CYBB gene, which encodes the 91-kD glycoprotein component (termed "gp91-phox") of the oxidase. We have identified the mutations in the CYBB gene responsible for X-linked CGD in 131 consecutive independent kindreds. Screening by SSCP analysis identified mutations in 124 of the kindreds, and sequencing of all exons and intron boundary regions revealed the other seven mutations. We detected 103 different specific mutations; no single mutation appeared in more than seven independent kindreds. The types of mutations included large and small deletions (11%), frameshifts (24%), nonsense mutations (23%), missense mutations (23%), splice-region mutations (17%), and regulatory-region mutations (2%). The distribution of mutations within the CYBB gene exhibited great heterogeneity, with no apparent mutational hot spots. Evaluation of 87 available mothers revealed X-linked carrier status in all but 10. The heterogeneity of mutations and the lack of any predominant genotype indicate that the disease represents many different mutational events, without a founder effect, as is expected for a disorder with a previously lethal phenotype.
authors.affiliation: Department of Immunology, Genetech, Inc., South San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rae
authors.forename: P E
authors.initials: PE
authors.lastname: Newburger
authors.forename: M C
authors.initials: MC
authors.lastname: Dinauer
authors.forename: D
authors.initials: D
authors.lastname: Noack
authors.forename: P J
authors.initials: PJ
authors.lastname: Hopkins
authors.forename: R
authors.initials: R
authors.lastname: Kuruto
authors.forename: J T
authors.initials: JT
authors.lastname: Curnutte
mesh_terms: D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D016897:Respiratory Burst / Q000235:genetics*; D014960:X Chromosome
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases