title: An in-frame triplet deletion within the gp91-phox gene in an adult X-linked chronic granulomatous disease patient with residual NADPH-oxidase activity.
abstract: In an adult patient suffering from X-linked chronic granulomatous disease (X-CGD) with residual activity of the NADPH-oxidase we found an unusual biochemical constellation with a defective gp91-phox gene. As shown by Western blot using a specific antibody the gp91-phox protein was normal in PMN. However, NADPH-oxidase activity was reduced and no heme spectrum was detectable. By Southern blot and RFLP analysis of genomic DNA a larger defect within the gp91-phox gene was excluded. Sequencing of the gp91-phox cDNA revealed an in-frame deletion of a TTC triplet in exon VI of the gp91-phox gene. This mutation indicates the loss of one amino acid (phenylalanine 215 or 216) in the gp91-phox protein. Sequencing of genomic DNA from the heterozygous daughter of the propositus confirmed this mutation. The absence of a functional cytochrome b558-spectrum in granulocytes of the patient suggests an involvement of the phenylalanine 216 area in heme binding by gp91 phox. This is the first mutation described in a X-CGD patient with absence of a functional cytochrome b558-spectrum but with detectable gp91-phox protein and residual NADPH-oxidase activity.
authors.affiliation: Universitätskinderklinik Göttingen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Jendrossek
authors.forename: A
authors.initials: A
authors.lastname: Ritzel
authors.forename: B
authors.initials: B
authors.lastname: Neubauer
authors.forename: S
authors.initials: S
authors.lastname: Heyden
authors.forename: M
authors.initials: M
authors.lastname: Gahr
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000906:Antibodies; D001424:Bacterial Infections; D003573:Cytochrome b Group / Q000097:blood; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D006580:Genetic Carrier Screening; D006098:Granulocytes / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D006418:Heme / Q000032:analysis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D008961:Models, Structural; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010375:Pedigree; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017384:Sequence Deletion; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014960:X Chromosome; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000906:Antibodies; D003573:Cytochrome b Group; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D013481:Superoxides; D006418:Heme; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; C036888:cytochrome b558; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate