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Gain-of-Function Mutations in IFIH1 Cause a Spectrum of Human Disease Phenotypes Associated with Upregulated Type I Interferon Signaling

2014Journal article Open access
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dc.contributor.authorRice, G
dc.contributor.authorToro Duany, Y
dc.contributor.authorJenkinson, E
dc.contributor.authorForte, G
dc.contributor.authorAnderson, B
dc.contributor.authorAriaudo, G
dc.contributor.authorBader-Meunier, B
dc.contributor.authorBaildam, E
dc.contributor.authorBattini, R
dc.contributor.authorBeresford, M
dc.contributor.authorCasarano, M
dc.contributor.authorChouchane, M
dc.contributor.authorCimaz, R
dc.contributor.authorCollins, AM
dc.contributor.authorCordeiro, N
dc.contributor.authorDale, R
dc.contributor.authorDavidson, J
dc.contributor.authorDe Waele, L
dc.contributor.authorDesguerre, I
dc.contributor.authorFaivre, L
dc.contributor.authorFazzi, E
dc.contributor.authorIsidor, B
dc.contributor.authorLagae, L
dc.contributor.authorLatchman, A
dc.contributor.authorLebon, P
dc.contributor.authorLi, C
dc.contributor.authorLivingston, J
dc.contributor.authorLourenço, C
dc.contributor.authorMancardi, MM
dc.contributor.authorMasurel-Paulet, A
dc.contributor.authorMcInnes, I
dc.contributor.authorMenezes, M
dc.contributor.authorMignot, C
dc.contributor.authorO’Sullivan, J
dc.contributor.authorOrcesi, S
dc.contributor.authorPicco, P
dc.contributor.authorRiva, E
dc.contributor.authorRobinson, R
dc.contributor.authorRodriguez, D
dc.contributor.authorSalvatici, E
dc.contributor.authorScott, C
dc.contributor.authorSzybowska, M
dc.contributor.authorTolmie, J
dc.contributor.authorVanderver, A
dc.contributor.authorVanhulle, C
dc.contributor.authorVieira, JP
dc.contributor.authorWebb, K
dc.contributor.authorWhitney, R
dc.contributor.authorWilliams, S
dc.contributor.authorWolfe, L
dc.contributor.authorM Zuberi, S
dc.contributor.authorHur, S
dc.contributor.authorCrow, Y
dc.date.accessioned2015-08-20T11:59:42Z
dc.date.available2015-08-20T11:59:42Z
dc.date.issued2014
dc.description.abstractThe type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer a gain-of-function - so that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.por
dc.identifier.citationNat Genet. 2014 ; 46(5): 503–509por
dc.identifier.urihttp://hdl.handle.net/10400.17/2274
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherNature Publishing Grouppor
dc.subjectInterferon Tipo Ipor
dc.subjectHDE NEU PEDpor
dc.titleGain-of-Function Mutations in IFIH1 Cause a Spectrum of Human Disease Phenotypes Associated with Upregulated Type I Interferon Signalingpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage509por
oaire.citation.startPage503por
oaire.citation.volume46por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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