Language:

Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling

Nature genetics, 2014-05, Vol.46 (5), p.503-509 [Peer Reviewed Journal]

COPYRIGHT 2014 Nature Publishing Group ;COPYRIGHT 2014 Nature Publishing Group ;Copyright Nature Publishing Group May 2014 ;ISSN: 1061-4036 ;EISSN: 1546-1718 ;DOI: 10.1038/ng.2933 ;PMID: 24686847

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling
Author: Rice, Gillian I ; Del Toro Duany, Yoandris ; Jenkinson, Emma M ; Forte, Gabriella Ma ; Anderson, Beverley H ; Ariaudo, Giada ; Bader-Meunier, Brigitte ; Baildam, Eileen M ; Battini, Roberta ; Beresford, Michael W ; Casarano, Manuela ; Chouchane, Mondher ; Cimaz, Rolando ; Collins, Abigail E ; Cordeiro, Nuno Jv ; Dale, Russell C ; Davidson, Joyce E ; De Waele, Liesbeth ; Desguerre, Isabelle ; Faivre, Laurence ; Fazzi, Elisa ; Isidor, Bertrand ; Lagae, Lieven ; Latchman, Andrew R ; Lebon, Pierre ; Li, Chumei ; Livingston, John H ; Lourenço, Charles M ; Mancardi, Maria Margherita ; Masurel-Paulet, Alice ; McInnes, Iain B ; Menezes, Manoj P ; Mignot, Cyril ; O'Sullivan, James ; Orcesi, Simona ; Picco, Paolo P ; Riva, Enrica ; Robinson, Robert A ; Rodriguez, Diana ; Salvatici, Elisabetta ; Scott, Christiaan ; Szybowska, Marta ; Tolmie, John L ; Vanderver, Adeline ; Vanhulle, Catherine ; Vieira, Jose Pedro ; Webb, Kate ; Whitney, Robyn N ; Williams, Simon G ; Wolfe, Lynne A ; Zuberi, Sameer M ; Hur, Sun ; Crow, Yanick J
Subjects: Analysis of Variance ; Autoimmune Diseases of the Nervous System - genetics ; Autoimmune Diseases of the Nervous System - immunology ; Base Sequence ; Biomedical research ; Cell receptors ; DEAD-box RNA Helicases - chemistry ; DEAD-box RNA Helicases - genetics ; Disease ; Electrophoretic Mobility Shift Assay ; Exome - genetics ; Families & family life ; Gene mutations ; Genetic aspects ; Genetic regulation ; Genomes ; Genotype & phenotype ; Health aspects ; HEK293 Cells ; Hospitals ; Humans ; Interferon ; Interferon Type I - immunology ; Interferon-Induced Helicase, IFIH1 ; Microsatellite Repeats - genetics ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Mutation - genetics ; Nervous System Malformations - genetics ; Nervous System Malformations - immunology ; Pathogenesis ; Phenotype ; Proteins ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Signal Transduction - genetics ; Spectrum Analysis ; Studies ; Womens health
Is Part Of: Nature genetics, 2014-05, Vol.46 (5), p.503-509
Description: 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 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 (also called MDA5) cause a spectrum of neuroimmunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer gain of function such 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1061-4036
EISSN: 1546-1718
DOI: 10.1038/ng.2933
PMID: 24686847
Source: GFMER Free Medical Journals
MEDLINE
ProQuest Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling

COPYRIGHT 2014 Nature Publishing Group ;COPYRIGHT 2014 Nature Publishing Group ;Copyright Nature Publishing Group May 2014 ;ISSN: 1061-4036 ;EISSN: 1546-1718 ;DOI: 10.1038/ng.2933 ;PMID: 24686847

Searching Remote Databases, Please Wait