title: Molecular analysis of chronic granulomatous disease caused by defects in gp91-phox.
abstract: Chronic granulomatous disease (CGD) is an uncommon inherited disorder of phagocytic cells in which a defective respiratory burst leads to severe recurrent bacterial and fungal infections. The disease is a consequence of mutations in one of the four molecules that constitute the NADPH oxidase system of electron transport, whose most critical component is an unusual flavocytochrome b localized in the plasma and specific granule membranes. Mutations in the CYBB gene (localized in the short arm of the X chromosome) encoding the beta-subunit of this flavocytochrome (gp91-phox), which is are responsible for 60-65% of all cases of CGD. In this paper, we report the molecular characterization of seven unrelated kindreds native from Colombia and Brazil with CGD caused by gp91-phox deficiency. The exons with the possible mutation were identified by single-strand conformational polymorphism (SSCP) of genomic DNA and then confirmed by DNA sequencing. In one patient we found a substitution of A to G in the penultimate nucleotide of intron 12 (IVS12-2A-->G). In four other cases, four different nonsense mutations were detected: R91X, W106X, R157X, and R290X and the other two patients showed missense substitutions: E225V and C244Y. In six of these kindreds, all mothers were carriers but one that did not present any change in the gp91-phox gene, which indicates a de novo mutation in this kindred. Then, these family-specific mutations in gp91-phox produce different structural defects that alter the expression or function of an essential component of phagocyte oxidase.
authors.affiliation: Laboratory of Immunology, School of Medicine, Universidad de Antioquia, Medellin, Columbia. ppatino@catios.udea.edu.co
authors.forename: P J
authors.initials: PJ
authors.lastname: Patiño
authors.forename: J E
authors.initials: JE
authors.lastname: Perez
authors.forename: J A
authors.initials: JA
authors.lastname: Lopez
authors.forename: A
authors.initials: A
authors.lastname: Condino-Neto
authors.forename: A S
authors.initials: AS
authors.lastname: Grumach
authors.forename: J H
authors.initials: JH
authors.lastname: Botero
authors.forename: J T
authors.initials: JT
authors.lastname: Curnutte
authors.forename: D
authors.initials: D
authors.lastname: García de Olarte
mesh_terms: D000293:Adolescent; D001938:Brazil / Q000208:ethnology; D002675:Child, Preschool; D003105:Colombia / Q000208:ethnology; D004252:DNA Mutational Analysis; D017931:DNA Primers; D008040:Genetic Linkage; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D020125:Mutation, Missense; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D018807:Polymorphism, Single-Stranded Conformational; D014960:X Chromosome
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases