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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1999-4-26
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pubmed:abstractText |
The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BCG Vaccine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:AltareFF,
pubmed-author:BraiMM,
pubmed-author:CasanovaJ LJL,
pubmed-author:ClarkeJJ,
pubmed-author:DöffingerRR,
pubmed-author:DormanS ESE,
pubmed-author:DucoulombierHH,
pubmed-author:DupuisSS,
pubmed-author:EdgarDD,
pubmed-author:EmileJ FJF,
pubmed-author:FischerAA,
pubmed-author:FondanècheM CMC,
pubmed-author:GirdlestoneJJ,
pubmed-author:HeyneKK,
pubmed-author:HollandS MSM,
pubmed-author:JouanguyEE,
pubmed-author:KumararatneD SDS,
pubmed-author:Lamhamedi-CherradiSS,
pubmed-author:LammasDD,
pubmed-author:NovelliVV,
pubmed-author:OxeliusV AVA,
pubmed-author:SchreiberR DRD
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pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
370-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10192386-Adolescent,
pubmed-meshheading:10192386-Adult,
pubmed-meshheading:10192386-B-Lymphocytes,
pubmed-meshheading:10192386-BCG Vaccine,
pubmed-meshheading:10192386-DNA-Binding Proteins,
pubmed-meshheading:10192386-Female,
pubmed-meshheading:10192386-Fibroblasts,
pubmed-meshheading:10192386-Gene Expression,
pubmed-meshheading:10192386-Genetic Predisposition to Disease,
pubmed-meshheading:10192386-Heterozygote,
pubmed-meshheading:10192386-Humans,
pubmed-meshheading:10192386-Interferon-gamma,
pubmed-meshheading:10192386-Male,
pubmed-meshheading:10192386-Mycobacterium,
pubmed-meshheading:10192386-Mycobacterium Infections,
pubmed-meshheading:10192386-Pedigree,
pubmed-meshheading:10192386-RNA, Messenger,
pubmed-meshheading:10192386-Receptors, Interferon,
pubmed-meshheading:10192386-STAT1 Transcription Factor,
pubmed-meshheading:10192386-Sequence Deletion,
pubmed-meshheading:10192386-Trans-Activators,
pubmed-meshheading:10192386-Transfection
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pubmed:year |
1999
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pubmed:articleTitle |
A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.
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pubmed:affiliation |
INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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