Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease

• Published in: Nature genetics Vol. 48; no. 1; pp. 67 - 73
• Main Authors: Zhou, Qing, Wang, Hongying, Schwartz, Daniella M, Stoffels, Monique, Park, Yong Hwan, Zhang, Yuan, Yang, Dan, Demirkaya, Erkan, Takeuchi, Masaki, Tsai, Wanxia Li, Lyons, Jonathan J, Yu, Xiaomin, Ouyang, Claudia, Chen, Celeste, Chin, David T, Zaal, Kristien, Chandrasekharappa, Settara C, P Hanson, Eric, Yu, Zhen, Mullikin, James C, Hasni, Sarfaraz A, Wertz, Ingrid E, Ombrello, Amanda K, Stone, Deborah L, Hoffmann, Patrycja, Jones, Anne, Barham, Beverly K, Leavis, Helen L, van Royen-Kerkof, Annet, Sibley, Cailin, Batu, Ezgi D, Gül, Ahmet, Siegel, Richard M, Boehm, Manfred, Milner, Joshua D, Ozen, Seza, Gadina, Massimo, Chae, JaeJin, Laxer, Ronald M, Kastner, Daniel L, Aksentijevich, Ivona
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2016; Nature Publishing Group
• Subjects: 45/23; 45/47; 45/77; 631/208/1516; 631/250/248; 692/699/249/2510; 82/1; 82/51; 82/80; Age of Onset; Agriculture; Animal Genetics and Genomics; Biomedicine; Blood proteins; Cancer Research; Cytokines; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Gene Function; Gene mutation; Genetic aspects; Haploinsufficiency - genetics; Hereditary Autoinflammatory Diseases - genetics; Hereditary Autoinflammatory Diseases - metabolism; Human Genetics; Humans; I-kappa B Kinase - genetics; I-kappa B Kinase - metabolism; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; Inflammation; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; letter; Male; Mutation; NF-kappa B - genetics; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pedigree; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Studies; TNF Receptor-Associated Factor 6 - genetics; TNF Receptor-Associated Factor 6 - metabolism; Translocation; Tumor Necrosis Factor alpha-Induced Protein 3; Tumor necrosis factor-TNF; Ubiquitin

Ivona Aksentijevich and colleagues identify heterozygous loss-of-function mutations in TNFAIP3 (encoding A20) in six unrelated families with early-onset systemic inflammation. Affected individuals exhibit increased expression of NF-κB–mediated proinflammatory cytokines, consistent with the establish...