Clinical features and genetic analysis of haploinsufficiency of A20 caused by heterozygous mutation in TNFAIP3 gene
Objective To explore the clinical manifestation,genetic characteristics,treatment and prognosis in a child with haploinsufficiency of A20(HA20).Methods The clinical data of a child with tumor necrosis factor α-induced protein 3(TNFAIP3)mutated HA20 was analyzed retrospectively in Children's Hospital Affiliated of Zhengzhou University.Peripheral blood mononuclear cells(PBMCs)were extracted from the patients'blood,and Western blot was used to detect the expression of A20 protein.Further literature review was done after searching articles in PubMed and Wanfang databases.Results A 5 years and 2 months old female patient,presented with recurrent fever,mouth ulcers,diarrhea and perianal abscess.The C-reactive protein(15.5 mg/L)and erythrocyte sedimentation rate(68 mm/h)was reported to be high.Colonoscopy showed congestion and swelling of the terminal ileum and colon mucosa,and multiple ulcers.The whole exome sequencing showed that the proband carried a heterozygous frameshift variant in the TNFAIP3 gene c.866delA(p.H289Pfs*3).The prediction re-sults of the tertiary structure of the protein indicated that variation might affect the spatial structure of protein.The expression of A20 Protein in PBMCs from patient was significantly decreased compared with her parents.So the variant leading to early stop codons was highly predicted to be deleterious.Conclusion HA20 is a rare monogenic autoinflammatory disease.The clinical phenotypes are complex.For patients with recurrent fever,oral ulcers and refractory diarrhea in early childhood,gene sequencing should be performed for early diagnosis.
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