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

Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity 1 .Herein we describe a new syndrome caused by high penetrance heterozygous germline mutations in the NFκB regulatory protein TNFAIP3 (A20) in six unrelated families with early onset systemic inflammation.The syndrome resembles Behçet's disease (BD), which is typically considered a polygenic disorder with onset in early adulthood 2 .A20 is a potent inhibitor of the NFκB signaling pathway 3 .TNFAIP3 mutant truncated proteins are likely to act by haploinsufficiency since they do