Article
Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.
Nature genetics - 1 Apr 2021
Wang Lin, Aschenbrenner Dominik, Zeng Zhiyang, Cao Xiya, Mayr Daniel, Mehta Meera, Capitani Melania, Warner Neil, Pan Jie, Wang Liren, Li Qi, Zuo Tao, Cohen-Kedar Sarit, Lu Jiawei, Ardy Rico Chandra, Mulder Daniel J, Dissanayake Dilan, Peng Kaiyue, Huang Zhiheng, Li Xiaoqin, Wang Yuesheng, Wang Xiaobing, Li Shuchao, Bullers Samuel, Gammage Anís N, Warnatz Klaus, Schiefer Ana-Iris, Krivan Gergely, Goda Vera, Kahr Walter H A, Lemaire Mathieu, Lu Chien-Yi, Siddiqui Iram, Surette Michael G, Kotlarz Daniel, Engelhardt Karin R, Griffin Helen R, Rottapel Robert, Decaluwe Hélène, Laxer Ronald M, Proietti Michele, Hambleton Sophie, Elcombe Suzanne, Guo Cong-Hui, Grimbacher Bodo, Dotan Iris, Ng Siew C, Freeman Spencer A, Snapper Scott B, Klein Christoph, Boztug Kaan, Huang Ying, Li Dali, Uhlig Holm H, Muise Aleixo M
Abstract excerpt
Spleen tyrosine kinase (SYK) is a critical immune signaling molecule and therapeutic target. We identified damaging monoallelic SYK variants in six patients with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. The SYK variants increased phosphorylation and enhanced downstream signaling, indicating gain of function. A knock-in...
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