TNFAIP3基因杂合缺失致A20单倍剂量不足一家系分析OA

The proband was a 3-year-4-month-old boy who had experienced recurrent diarrhea,fever,joint swelling and pain for more than a year accompanied by oral and perianal ulcers.Gastrointestinal endoscopy revealed multiple colorectal ulcers.The proband's 36-year-old father had a three-year history of oral ulcers and a one-year history of recurrent diarrhea;gastroscopy showed chronic non-atrophic gastritis with erosion and duodenitis,while colonoscopy was unremarkable.Whole exome sequencing revealed that the proband and his parents had no pathogenic single nucleotide variants or small insertions/deletions.Subsequent copy number variation analysis identified a heterozygous deletion of exons 2-9 in the tumor necrosis factor-α-induced protein 3(TNFAIP3)gene in both the proband and his father,which was confirmed by quantitative PCR.Based on the clinical manifestations and genetic findings,the proband and his father were diagnosed with haploinsufficiency of A20(HA20).Therefore,in patients with suspected HA20 presenting early-onset Behçet's syndrome-like manifestations,copy number variation analysis should be performed when whole exome sequencing fails to detect single nucleotide variants or small insertions/deletions in the TNFAIP3 gene.