title: Point mutations in the beta-subunit of cytochrome b558 leading to X-linked chronic granulomatous disease.
abstract: The NADPH:O2 oxidoreductase of phagocytic leukocytes is an important enzyme for the bactericidal activity of these cells. Cytochrome b558 is a membrane component of this enzyme. In X-linked chronic granulomatous disease (Xb- CGD) the phagocytes are defective in the beta-subunit (gp91-phox) of this cytochrome. We have studied the genetic defect in a group of six X-linked CGD patients characterized by complete or partial loss of cytochrome b558 with the use of the polymerase chain reaction. All patients had a different single point mutation in the gp91-phox gene, indicating that the genetic defect in Xb- CGD is very heterogeneous. In one patient the mutation leads to a premature termination codon. In the other five cases these mutations predict incorporation of a different amino acid. The mutations were with one exception found in the N-terminal half of the protein, suggesting that this part of cytochrome b558 is important for the binding of the heme or for formation of a stable complex with p22-phox. Two histidyl residues were found that might be ligands of the heme iron.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: B G
authors.initials: BG
authors.lastname: Bolscher
authors.forename: M
authors.initials: M
authors.lastname: de Boer
authors.forename: A
authors.initials: A
authors.lastname: de Klein
authors.forename: R S
authors.initials: RS
authors.lastname: Weening
authors.forename: D
authors.initials: D
authors.lastname: Roos
mesh_terms: D000483:Alleles; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015153:Blotting, Western; D003573:Cytochrome b Group / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D019255:NADPH Oxidases; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014960:X Chromosome
chemical_list: D000911:Antibodies, Monoclonal; D003573:Cytochrome b Group; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D012313:RNA; D004247:DNA; C036888:cytochrome b558; D019255:NADPH Oxidases