Autosomal dominant Hashimoto’s thyroiditis with a mutation in TNFAIP3

Abstract. Hashimoto’s thyroiditis (HT) is an autoimmune disease thought to involve a combination of genetic and environmental factors, but its detailed pathogenesis is unknown. We present a family with haploinsufficiency of the gene encoding tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) and show a link with HT in a three-generation pedigree. Currently, TNFAIP3 polymorphisms are associated with several autoimmune diseases, and haploinsufficiency of A20 was recently observed in families with an early-onset autoinflammatory disease resembling Behçet’s disease. However, HT has not been linked with TNFAIP3 variants. We analyzed TNFAIP3 and human leukocyte antigen (HLA) in the family showing HT as an autosomal dominant trait, and identified a novel heterozygous c.2209delC mutation of TNFAIP3 in the members with HT. The known HLA haplotypes linked to HT could not be identified. Based on our analysis of this pedigree, we consider HT as a possible phenotype of A20 haploinsufficiency.