Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.17/2274
Título: Gain-of-Function Mutations in IFIH1 Cause a Spectrum of Human Disease Phenotypes Associated with Upregulated Type I Interferon Signaling
Autor: Rice, G
Toro Duany, Y
Jenkinson, E
Forte, G
Anderson, B
Ariaudo, G
Bader-Meunier, B
Baildam, E
Battini, R
Beresford, M
Casarano, M
Chouchane, M
Cimaz, R
Collins, AM
Cordeiro, N
Dale, R
Davidson, J
De Waele, L
Desguerre, I
Faivre, L
Fazzi, E
Isidor, B
Lagae, L
Latchman, A
Lebon, P
Li, C
Livingston, J
Lourenço, C
Mancardi, MM
Masurel-Paulet, A
McInnes, I
Menezes, M
Mignot, C
O’Sullivan, J
Orcesi, S
Picco, P
Riva, E
Robinson, R
Rodriguez, D
Salvatici, E
Scott, C
Szybowska, M
Tolmie, J
Vanderver, A
Vanhulle, C
Vieira, JP
Webb, K
Whitney, R
Williams, S
Wolfe, L
M Zuberi, S
Hur, S
Crow, Y
Palavras-chave: Interferon Tipo I
HDE NEU PED
Data: 2014
Editora: Nature Publishing Group
Citação: Nat Genet. 2014 ; 46(5): 503–509
Resumo: The 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.
Peer review: yes
URI: http://hdl.handle.net/10400.17/2274
Aparece nas colecções:NEU PED - Artigos

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