[A family of tumor necrosis factor receptor-associated periodic syndrome].

Abstract

Objective: To analyze the clinical manifestations and gene variations of tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Methods: Clinical data and gene testing of four children and three adult relatives in a family from Puning, Guangdong were retrospectively analyzed. CD4(+)T cells, CD8(+)T cells, B cells, monocytes and NK cells were assessed by flow cytometry. Plasma level of TNFR receptors were assessed by enzyme linked immunosorbent assay (ELISA). TNFRSF1A gene variation was identified by second generation sequencing. Swiss-Model was used to analyze the potential impact of TNFRSF1A gene variation on its protein tertiary structure. Results: For all the patients,periodic fever was the main clinical feature,combined with arthralgia,myalgia,multiple serositis,periorbital edema and migratory cutaneous rash,accompanied with elevated level of acute-phase reactants and increased white blood cell counts during each episode. This disease was found in both gender and every generation in this family. The median age of onset was 2 years, ranging from 6 months to 30 years. The plasma level of TNFR1 of the patients range from 0 to 12.4 ng/L,which was lower than that of the normal controls range from 18.0~22.2 ng/L,while the level of TNFR2 was normal. Also, the numbers of T cells, B cells and monocytes were within normal range; however,number of NK cells in the patients (0.070±0.034) was lower than that in the normal controls (0.152±0.122). The TNFRSF1A variation,located in exon 3: c.295T>A (p.C99S),was found in the proband as well as the other 6 family members,which could induce change of the side chain of amino acid according to the prediction of the three-dimensional structure,subsequently affecting the binding to the receptor. Conclusions: TRAPS is characterized by periodic fever,arthralgia,myalgia,multiple serositis,periorbital edema and migratory cutaneous rash,with a significant decrease in plasma level of TNFR1 and NK cells. The gene sequencing analysis revealed a pathogenic variation in TNFRSF1A gene.