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dc.contributor.authorNewburger, Peter E.
dc.contributor.authorMalawista, Stephen E.
dc.contributor.authorDinauer, Mary C.
dc.contributor.authorGelbart, Terri
dc.contributor.authorWoodman, Richard C.
dc.contributor.authorChada, Sunil
dc.contributor.authorShen, Qichang
dc.contributor.authorvan Blaricom, Gretchen
dc.contributor.authorQuie, Paul G.
dc.contributor.authorCurnutte, John T.
dc.date2022-08-11T08:09:46.000
dc.date.accessioned2022-08-23T16:42:47Z
dc.date.available2022-08-23T16:42:47Z
dc.date.issued1994-12-01
dc.date.submitted2008-04-14
dc.identifier.citationBlood. 1994 Dec 1;84(11):3861-9.
dc.identifier.issn0006-4971 (Print)
dc.identifier.pmid7949143
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40161
dc.description.abstractWe have restudied two kindreds that formed the basis of the original report of autosomal recessive chronic granulomatous disease (CGD) associated with leukocyte glutathione peroxidase deficiency. Case 1 from the original study and the surviving brother of the originally reported case 2 both have severe CGD, with no detectable respiratory burst activity in purified intact neutrophils. However, their leukocytes exhibit normal glutathione peroxidase enzyme activity and gene expression. Examination of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase components known to be defective in CGD reveals no detectable cytochrome b558 nor any membrane activity in a cell-free NADPH oxidase assay system. Molecular analysis of the genes encoding cytochrome b558 subunits shows, in case 1, a C-->T substitution at nucleotide 688 of the gene encoding the gp91-phox subunit of cytochrome b558, resulting in a termination signal in place of Arginine-226. Levels of gp91-phox mRNA are markedly decreased despite normal levels of gene transcription, indicating a post-transcriptional effect of the nonsense mutation on mRNA processing or stability. The X-linked form of CGD developed in this cytogenetically normal female due to the uniform inactivation of the normal X chromosome in her granulocytes, indicated by the expression in her granulocyte mRNA of only one allele of a glucose-6-phosphate dehydrogenase polymorphisms for which she is heterozygous in genomic DNA. Case 2 (of the present study) has distinct mutations in each allele of the p22-phox gene.(ABSTRACT TRUNCATED AT 250 WORDS)
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7949143&dopt=Abstract ">Link to article in PubMed</a>
dc.subjectAdult
dc.subjectBase Sequence
dc.subjectCytochrome b Group
dc.subjectFemale
dc.subjectGenes
dc.subjectGenes, Recessive
dc.subjectGlutathione Peroxidase
dc.subjectGranulomatous Disease, Chronic
dc.subjectHumans
dc.subjectInfant, Newborn
dc.subjectLinkage (Genetics)
dc.subjectMale
dc.subjectMembrane Glycoproteins
dc.subjectMolecular Sequence Data
dc.subjectNADH, NADPH Oxidoreductases
dc.subjectNADPH Oxidase
dc.subjectNeutrophils
dc.subjectPedigree
dc.subjectRespiratory Burst
dc.subjectMedical Genetics
dc.subjectMedical Microbiology
dc.subjectMedical Molecular Biology
dc.subjectPediatrics
dc.titleChronic granulomatous disease and glutathione peroxidase deficiency, revisited
dc.typeJournal Article
dc.source.journaltitleBlood
dc.source.volume84
dc.source.issue11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1295&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/296
dc.identifier.contextkey489634
refterms.dateFOA2022-08-23T16:42:47Z
html.description.abstract<p>We have restudied two kindreds that formed the basis of the original report of autosomal recessive chronic granulomatous disease (CGD) associated with leukocyte glutathione peroxidase deficiency. Case 1 from the original study and the surviving brother of the originally reported case 2 both have severe CGD, with no detectable respiratory burst activity in purified intact neutrophils. However, their leukocytes exhibit normal glutathione peroxidase enzyme activity and gene expression. Examination of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase components known to be defective in CGD reveals no detectable cytochrome b558 nor any membrane activity in a cell-free NADPH oxidase assay system. Molecular analysis of the genes encoding cytochrome b558 subunits shows, in case 1, a C-->T substitution at nucleotide 688 of the gene encoding the gp91-phox subunit of cytochrome b558, resulting in a termination signal in place of Arginine-226. Levels of gp91-phox mRNA are markedly decreased despite normal levels of gene transcription, indicating a post-transcriptional effect of the nonsense mutation on mRNA processing or stability. The X-linked form of CGD developed in this cytogenetically normal female due to the uniform inactivation of the normal X chromosome in her granulocytes, indicated by the expression in her granulocyte mRNA of only one allele of a glucose-6-phosphate dehydrogenase polymorphisms for which she is heterozygous in genomic DNA. Case 2 (of the present study) has distinct mutations in each allele of the p22-phox gene.(ABSTRACT TRUNCATED AT 250 WORDS)</p>
dc.identifier.submissionpathoapubs/296
dc.contributor.departmentDepartment of Pediatrics
dc.contributor.departmentDepartment of Molecular Genetics/Microbiology
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages3861-9


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