{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:01:36Z","timestamp":1790413296703,"version":"4.1.0"},"reference-count":26,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any one of 4 genes encoding phagocyte NADPH oxidase subunits. Unlike other CGD subtypes, in which there is great heterogeneity among mutations, 97% of affected alleles in patients previously reported with A470 CGD carry a single mutation, a GT deletion (\u0394GT) in exon 2 of the p47-phox gene, NCF-1. This unusually high incidence results from recombination events between NCF-1and its highly homologous pseudogenes, in which \u0394GT originates. In 50 consecutive patients with A470 CGD, 4 were identified who were heterozygous for \u0394GT in NCF-1, and for the first time, 2 were identified whose DNA appeared normal at this position. To avoid co-amplification of pseudogene sequence and to enable the identification of mutations in these patients, allele-specific polymerase chain reaction was used to amplify alleles not containing \u0394GT. In each of the 4 patients who were heterozygous for \u0394GT, an additional novel mutation was identified. These were 2 missense mutations, G125 \u2192 A in exon 2 (predicting Arg42 \u2192 Gln) and G784 \u2192 A in exon 8 (Gly262 \u2192 Ser), and 2 splice junction mutations at the 5\u2032 end of intron 1, gt \u2192 at and gtg \u2192 gtt. The first of 2 patients who appeared normal at the GT position was a compound heterozygote with the G125 \u2192 A transition on one allele and a deletion of G811 on the other. In the second of these patients, only a single defect was detected, G574 \u2192 A, which predicts Gly192 \u2192 Ser but is likely to result in defective splicing because it represents the final nucleotide of exon 6.<\/jats:p>","DOI":"10.1182\/blood.v97.1.305","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"305-311","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":75,"title":["Autosomal recessive chronic granulomatous disease caused by defects in NCF-1, the gene encoding the phagocyte p47-phox: mutations not arising in theNCF-1 pseudogenes"],"prefix":"10.1182","volume":"97","author":[{"given":"Deborah","family":"Noack","sequence":"first","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Rae","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Cross","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly A.","family":"Ellis","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Newburger","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Curnutte","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Heyworth","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; the Department of Immunology, Genentech, San Francisco, CA; and the Departments of Pediatrics and Molecular Genetics\/Microbiology, University of Massachusetts Medical School, Worcester, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021215383477500_B1","first-page":"353","article-title":"Chronic granulomatous disease.","volume-title":"Primary immunodeficiency diseases, a molecular and genetic approach.","author":"Roos","year":"1999"},{"key":"2020021215383477500_B2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/jlb.60.6.677","article-title":"Assembly of the phagocyte NADPH oxidase: molecular interaction of oxidase proteins.","volume":"60","author":"DeLeo","year":"1996","journal-title":"J Leukoc Biol."},{"key":"2020021215383477500_B3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/BF01454021","article-title":"The NADPH oxidase complex of phagocytic leukocytes: a biochemical and cytochemical view.","volume":"103","author":"Robinson","year":"1995","journal-title":"Histochemistry."},{"key":"2020021215383477500_B4","doi-asserted-by":"crossref","first-page":"S309","DOI":"10.1086\/513849","article-title":"Activation of the neutrophil respiratory burst oxidase.","volume":"179","author":"Clark","year":"1999","journal-title":"J Infect Dis."},{"key":"2020021215383477500_B5","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1182\/blood.V87.5.1663.1663","article-title":"Mutations in the X-linked and autosomal recessive forms of chronic granulomatous disease.","volume":"87","author":"Roos","year":"1996","journal-title":"Blood."},{"key":"2020021215383477500_B6","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1086\/301874","article-title":"X-linked chronic granulomatous disease: mutations in the CYBB gene encoding the gp91-phox component of respiratory-burst oxidase.","volume":"62","author":"Rae","year":"1998","journal-title":"Am J Hum Genet."},{"key":"2020021215383477500_B7","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1182\/blood.V94.7.2505.419k10_2505_2514","article-title":"Molecular characterization of autosomal recessive chronic granulomatous disease caused by a defect of the NADPH oxidase component p67-phox.","volume":"94","author":"Patin\u0303o","year":"1999","journal-title":"Blood."},{"key":"2020021215383477500_B8","first-page":"460","article-title":"Autosomal recessive chronic granulomatous disease caused by novel mutations in NCF-2, the gene encoding the p67-phox component of phagocyte oxidase.","volume":"105","author":"Noack","year":"1999","journal-title":"Hum Genet."},{"key":"2020021215383477500_B9","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1182\/blood.V96.3.1106","article-title":"Molecular analysis of nine new families with chronic granulomatous disease caused by mutations in CYBA, the gene encoding p22-phox.","volume":"96","author":"Rae","year":"2000","journal-title":"Blood."},{"key":"2020021215383477500_B10","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1073\/pnas.88.7.2753","article-title":"Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat.","volume":"88","author":"Casimir","year":"1991","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021215383477500_B11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1172\/JCI116171","article-title":"In vitro molecular reconstitution of the respiratory burst in B lymphoblasts from p47-phox\u2013deficient chronic granulomatous disease.","volume":"91","author":"Volpp","year":"1993","journal-title":"J Clin Invest."},{"key":"2020021215383477500_B12","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1006\/bbrc.1994.1382","article-title":"Homologous dinucleotide (GT or TG) deletion in Japanese patients with chronic granulomatous disease with p47-phox deficiency.","volume":"199","author":"Iwata","year":"1994","journal-title":"Biochem Biophys Res Commun."},{"key":"2020021215383477500_B13","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1182\/blood.V95.6.2150","article-title":"Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease.","volume":"95","author":"Roesler","year":"2000","journal-title":"Blood."},{"key":"2020021215383477500_B14","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1172\/JCI119721","article-title":"A p47-phox pseudogene carries the most common mutation causing p47-phox\u2013deficient chronic granulomatous disease.","volume":"100","author":"Go\u0308rlach","year":"1997","journal-title":"J Clin Invest."},{"key":"2020021215383477500_B15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1182\/blood.V62.3.564.564","article-title":"Impaired granulocyte superoxide production and prolongation of the respiratory burst due to a low-affinity NADPH-dependent oxidase.","volume":"62","author":"Shurin","year":"1983","journal-title":"Blood."},{"key":"2020021215383477500_B16","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1172\/JCI113360","article-title":"Chronic granulomatous disease due to a defect in the cytosolic factor required for nicotinamide adenine dinucleotide phosphate oxidase activation.","volume":"81","author":"Curnutte","year":"1988","journal-title":"J Clin Invest."},{"key":"2020021215383477500_B17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1182\/blood.V55.1.85.85","article-title":"Activity and activation of the granulocyte superoxide generating system.","volume":"55","author":"Newburger","year":"1980","journal-title":"Blood."},{"key":"2020021215383477500_B18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/0006-291X(82)92073-3","article-title":"Cytochalasin E diminishes the lag phase in the release of superoxide by human neutrophils.","volume":"106","author":"Badwey","year":"1982","journal-title":"Biochem Biophys Res Commun."},{"key":"2020021215383477500_B19","doi-asserted-by":"crossref","first-page":"8194","DOI":"10.1074\/jbc.270.14.8194","article-title":"A variant X-linked chronic granulomatous disease patient (X91+) with partially functional cytochrome b.","volume":"270","author":"Cross","year":"1995","journal-title":"J Biol Chem."},{"key":"2020021215383477500_B20","doi-asserted-by":"crossref","first-page":"30749","DOI":"10.1016\/S0021-9258(18)47341-3","article-title":"Rac translocates independently of the neutrophil NADPH oxidase components p47-phox and p67-phox: evidence for its interaction with flavocytochrome b558.","volume":"269","author":"Heyworth","year":"1994","journal-title":"J Biol Chem."},{"key":"2020021215383477500_B21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1006\/geno.1999.5815","article-title":"A complete physical contig and partial transcript map of the Williams syndrome critical region.","volume":"58","author":"Hockenhull","year":"1999","journal-title":"Genomics."},{"key":"2020021215383477500_B22","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1101\/gr.9.5.428","article-title":"Comparative mapping of the region of human chromosome 7 deleted in Williams syndrome.","volume":"9","author":"DeSilva","year":"1999","journal-title":"Genome Res."},{"key":"2020021215383477500_B23","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1093\/nar\/15.17.7155","article-title":"RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression.","volume":"15","author":"Shapiro","year":"1987","journal-title":"Nucleic Acids Res."},{"key":"2020021215383477500_B24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF00210743","article-title":"The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences.","volume":"90","author":"Krawczak","year":"1992","journal-title":"Hum Genet."},{"key":"2020021215383477500_B25","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1182\/blood.V80.6.1553.1553","article-title":"Splice site mutations are a common cause of X-linked chronic granulomatous disease.","volume":"80","author":"De Boer","year":"1992","journal-title":"Blood."},{"key":"2020021215383477500_B26","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/359851a0","article-title":"Crystal structure of a Src-homology 3 (SH3) domain.","volume":"359","author":"Musacchio","year":"1992","journal-title":"Nature."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/1\/305\/1670962\/305.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/1\/305\/1670962\/305.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T06:41:53Z","timestamp":1704523313000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/97\/1\/305\/52984\/Autosomal-recessive-chronic-granulomatous-disease"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,1,1]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v97.1.305","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2001,1,1]]}}}