Dataset Information


Severe type 1 interferonopathy due to germline STAT2 gain-of-function

ABSTRACT: The transcription factor STAT2 is essential for transcriptional activation downstream of the receptors for the innate IFNs -α/β (IFNAR) and -gamma (IFNLR). STAT2 is activated by tyrosine phosphorylation, associating with STAT1 and IRF9 to form the Interferon-Stimulated Gene Factor 3 (ISGF3) to effect gene transcription. Loss-of-function variants in STAT2 increase susceptibility to viral disease. Here a transcriptome study is reported on an individual with severe early-onset neuroinflammatory disease and an elevated IFN signature. The individual had a homozygous missense variant in STAT2 and symptoms consistent with a gain-of-function effect.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens  

DISEASE(S): Interferonopathy,Normal


PROVIDER: E-MTAB-7275 | ArrayExpress | 2019-11-06



Dataset's files

Action DRS
E-MTAB-7275.idf.txt Idf
E-MTAB-7275.idf.txt_original Idf
E-MTAB-7275.sdrf.txt Txt
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Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2.

Duncan Christopher J A CJA   Thompson Benjamin J BJ   Chen Rui R   Rice Gillian I GI   Gothe Florian F   Young Dan F DF   Lovell Simon C SC   Shuttleworth Victoria G VG   Brocklebank Vicky V   Corner Bronte B   Skelton Andrew J AJ   Bondet Vincent V   Coxhead Jonathan J   Duffy Darragh D   Fourrage Cecile C   Livingston John H JH   Pavaine Julija J   Cheesman Edmund E   Bitetti Stephania S   Grainger Angela A   Acres Meghan M   Innes Barbara A BA   Mikulasova Aneta A   Sun Ruyue R   Hussain Rafiqul R   Wright Ronnie R   Wynn Robert R   Zarhrate Mohammed M   Zeef Leo A H LAH   Wood Katrina K   Hughes Stephen M SM   Harris Claire L CL   Engelhardt Karin R KR   Crow Yanick J YJ   Randall Richard E RE   Kavanagh David D   Hambleton Sophie S   Briggs Tracy A TA  

Science immunology 20191201 42

Excessive type I interferon (IFNα/β) activity is implicated in a spectrum of human disease, yet its direct role remains to be conclusively proven. We investigated two siblings with severe early-onset autoinflammatory disease and an elevated IFN signature. Whole-exome sequencing revealed a shared homozygous missense Arg148Trp variant in STAT2, a transcription factor that functions exclusively downstream of innate IFNs. Cells bearing STAT2R148W in homozygosity (but not heterozygosity) were hyperse  ...[more]

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