A novel missense variant in TNFAIP3 associated with autoimmunity reveals the contribution of STAT1/mTOR pathways.

ABSTRACT: Heterozygous loss-of-function mutations in the TNFAIP3 gene lead to A20 haploinsufficiency (HA20). A20 protein is a negative feedback regulator of NF-κB signaling. Traditionally, HA20 is associated with Behçet's disease-like symptoms, however, recent findings suggest it may also manifest with a broader array of autoimmune diseases. Here, we describe a novel TNFAIP3 variant in a Dutch family, predominantly presenting with polyautoimmunity rather than autoinflammatory manifestations. We evaluated two patients from a Dutch family with autoimmune symptoms. Whole-exome sequencing (WES) identified a heterozygous c.608T>G (p.Leu203Arg) missense variant in TNFAIP3, located within the OTU domain. Functional analyses included immunoblotting of peripheral blood mononuclear cells (PBMCs) and an overex

SUBMITTER: Potjewijd J 

PROVIDER: S-EPMC12457938 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature