Haploinsufficiency of A20 in a family caused by a heterozygous deletion in the TNFAIP3 gene

The proband in this family was a 3.3-year-old boy who had been ill for over 1 year, presenting with recurrent diarrhea, fever, joint swelling and pain, accompanied by oral ulcers and perianal ulcers. Gastrointestinal endoscopy revealed multiple colorectal ulcers. The proband's father, a 36-year-old male, had a history of oral ulcers for over 3 years and recurrent diarrhea for over 1 year; gastrointestinal endoscopy showed chronic non-atrophic gastritis with erosion and duodenitis. No pathogenic single-nucleotide variants or small indels were detected in the proband and his parents by whole-exome sequencing. Subsequent copy number variations analysis based on whole-exome sequencing identified a heterozygous deletion of exons 2-9 in TNFAIP3 in both the proband and his father, which was verified by qPCR. Based on the clinical manifestations and genetic testing results, the proband and his father were diagnosed with haploinsufficiency of A20 (HA20). We propose that copy number variations analysis in TNFAIP3 should be included in the genetic testing for patients with early-onset Behçet-like manifestations, especially when suspecting HA20.