Missense Mutations in the gp91-phox Gene Encoding Cytochromeb558 in Patients With Cytochrome b Positive and Negative X-Linked Chronic Granulomatous Disease
| Autor: | Hitoshi Sakuraba, Mizuho Kaneda, Akira Ohtake, Chika Kiryu, Akira Nishida, Katsuko Kakinuma |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities X Chromosome Heme binding Cytochrome Genetic Linkage Neutrophils Immunology Mutation Missense Biology Granulomatous Disease Chronic medicine.disease_cause Polymerase Chain Reaction Biochemistry chemistry.chemical_compound Chronic granulomatous disease Superoxides hemic and lymphatic diseases medicine Humans Missense mutation Child Heme Genetics Phagocytes Oxidase test Mutation Membrane Glycoproteins Point mutation NADPH Dehydrogenase Membrane Transport Proteins NADPH Oxidases DNA Cell Biology Hematology Cytochrome b Group Phosphoproteins medicine.disease chemistry Spectrophotometry NADPH Oxidase 2 biology.protein |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v93.6.2098.406k09_2098_2104 |
| Popis: | Chronic granulomatous disease (CGD) is a disorder of host defense due to genetic defects of the superoxide (O2-) generating NADPH oxidase in phagocytes. A membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22-phox, is a critical component of the oxidase. The X-linked form of the disease is due to defects in the gp91-phox gene. We report here biochemical and genetic analyses of patients with typical and atypical X-linked CGD. Immunoblots showed that neutrophils from one patient had small amounts of p22-phoxand gp91-phox and a low level of O2-forming oxidase activity, in contrast to the complete absence of both subunits in two patients with typical CGD. Using polymerase chain reactions (PCR) on cDNA and genomic DNA, we found novel missense mutations of gp91-phox in the two typical patients and a point mutation in the variant CGD, a characteristic common to two other patients with similar variant CGD reported previously. Spectrophotometric analysis of the neutrophils from the variant patient provided evidence for the presence of heme of cytochromeb558. Recently, we reported another variant CGD with similar amounts of both subunits, but without oxidase activity or the heme spectrum. A predicted mutation at amino acid 101 in gp91-phox was also confirmed in this variant CGD by PCR of the genomic DNA. These results on four patients, including those with two variant CGD, are discussed with respect to the missense mutated sites and the heme binding ligands in gp91-phox. |
| Databáze: | OpenAIRE |
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