Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease

被引：385

作者：

Flanagan, Sarah E. ^{[1
]}

Haapaniemi, Emma ^{[2
,3
]}

Russell, Mark A. ^{[1
]}

Caswell, Richard ^{[1
]}

Allen, Hana Lango ^{[1
]}

De Francol, Elisa ^{[1
]}

McDonald, Timothy J. ^{[1
]}

Rajala, Hanna ^{[4
,5
]}

Ramelius, Anita ^{[6
,7
]}

Barton, John ^{[8
]}

Heiskanen, Kaarina ^{[3
,9
]}

Heiskanen-Kosmal, Tarja ^{[10
]}

Kajosaari, Merja

Murphyli, Nuala P. ^{[11
]}

Milenkovic, Tatjana ^{[12
]}

Seppanen, Mikko ^{[13
]}

Lemmark, Ake ^{[6
,7
]}

Mustjoki, Satu ^{[5
]}

Otonkoski, Timo ^{[3
]}

Kere, Juha ^{[9
,14
,15
]}

Morgan, Noel G. ^{[1
]}

Ellard, Sian ^{[1
,2
]}

Hattersley, Andrew T. ^{[1
]}

机构：

[1] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England

[2] Univ Helsinki, Folkhalsan Inst Genet, Helsinki, Finland

[3] Univ Helsinki, Res Programs Unit, Helsinki, Finland

[4] Univ Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Helsinki, Finland

[5] Univ Helsinki, Cent Hosp, Ctr Canc, Helsinki, Finland

[6] Lund Univ, Dept Clin Sci, Lund, Sweden

[7] Skane Univ Hosp, Clin Res Ctr, Malmo, Sweden

[8] Bristol Royal Hosp Children, Bristol, Avon, England

[9] Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki, Finland

[10] Kuopio Univ Hosp, Dept Pediat, Helsinki, Finland

[11] Childrens Univ Hosp, Dept Endocrinol & Diabet, Dublin, Ireland

[12] Inst Mother & Child Hlth Care Serbia Dr Vukan Cup, Dept Endocrinol, Belgrade, Serbia

[13] Univ Helsinki, Cent Hosp, Div Infect Dis, Immunodeficiency Unit, Helsinki, Finland

[14] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden

[15] Karolinska Inst, Ctr Innovat Med, Huddinge, Sweden

来源：

NATURE GENETICS | 2014年 / 46卷 / 08期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; HYPER IGE SYNDROME; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; TH17; CELLS; VARIANTS; RISK;

D O I：

10.1038/ng.3040

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

引用

页码：812 / 814

页数：3

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