title: A new mutation in exon 12 of the gp91-phox gene leading to cytochrome b-positive X-linked chronic granulomatous disease.
abstract: We have previously reported a patient with cytochrome b-positive X-linked chronic granulomatous disease. Although the O2- production of neutrophils from the patient was completely defective, we presented data suggesting that the patient's cytochrome b was present at a normal level and possibly had normal spectroscopic features. Thus, to look for a mutation in the cytochrome b heavy chain (gp91-phox) gene, DNA analysis of gp91-phox cDNA derived from this patient was performed. As a result, we found that five nucleotides (1521 through 1525) within exon 12 were deleted, and a new sequence of eight nucleotides was inserted. This mutation converted Gln507-Lys508-Thr509 into His-Ile-Trp-Ala. Mismatched polymerase chain reaction showed that the mother has both wild and mutated alleles, confirming that this case was transmitted in an X-linked fashion. This mutation is different from those previously reported by others. The translocation of p47-phox and p67-phox to the membrane fraction occurred, indicating the complete formation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. We conclude that this case suggests that the structure encoded on exon 12 of gp91-phox is important for electron transfer.
authors.affiliation: Department of Pediatrics, Asahikawa Medical School, Hokkaido, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Oomi
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: I
authors.initials: I
authors.lastname: Kawabata
authors.forename: T
authors.initials: T
authors.lastname: Sakaino
authors.forename: S
authors.initials: S
authors.lastname: Koyano
authors.forename: T
authors.initials: T
authors.lastname: Suzutani
authors.forename: H
authors.initials: H
authors.lastname: Nunoi
authors.forename: A
authors.initials: A
authors.lastname: Okuno
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D003573:Cytochrome b Group / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004579:Electron Transport; D005091:Exons / Q000235:genetics*; D005260:Female; D005796:Genes; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000235:genetics*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009504:Neutrophils / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D016897:Respiratory Burst; D017384:Sequence Deletion; D014960:X Chromosome
chemical_list: D003573:Cytochrome b Group; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase