Tumor necrosis factor receptor associated periodic fever syndrome (TRAPS) is caused by heterozygote mutations in TNFRSF1A, characterized by recurrent inflammatory attacks.

In this report, we described two patients with different heterozygote mutations in TNFRSF1A. Patient 1, a 15-year-old male, had suffered from recurrent fever attacks accompanied by abdominal pain, eye manifestations, and myalgia with increased acute phase reactants since the age of 6-month. He had been unsuccessfully treated with colchicine for having familial Mediterranean fever without an identifiable MEFV mutation since the age of 4-year. At the age of 15 years, he was diagnosed with immunoglobulin (Ig) A nephropathy due to massive proteinuria and renal biopsy findings. Next generation sequencing revealed NM_001065.3: c.236C>T; p. (Thr79Met); T50M heterozygote mutation in TNFRFS1A. He was treated with methylprednisolone and cyclosporine for IgA nephropathy, thereafter with canakinumab for TRAPS. Patient 2, a 17-year-old female, had recurrent arthritis attacks accompanied by increased acute phase reactants for the last two months. She had neither fever attacks nor rashes or myalgia. Her physical examination was normal between attacks. Magnetic resonance imaging of both knees and ankles showed no signs of chronic arthritis. MEFV analyzes showed no mutation. Next generation sequencing revealed NM_001065.3: c.362G>A; p.(Arg121Gln); R92Q heterozygote mutation in TNFRFS1A. Arthritis attacks were treated successfully with ibuprofen thereafter.

In conclusion, we wish to emphasize the diversity of the clinical manifestations between these two patients with distinct sequence variants in TNFRSF1A. Moreover, we presented a rare manifestation of TRAPS, IgA nephropathy.

肿瘤坏死因子受体相关的周期性发热综合征（TRAPS）是由TNFRSF1A中的杂合子突变引起的，其特征为反复发炎性发作。

在本报告中，我们描述了两名在TNFRSF1A中具有不同杂合子突变的患者。患者1（15岁，男性）自6个月大以来就反复发作发烧，并伴有腹痛，眼部症状和肌痛，急性期反应物增多。自4岁以来，他因未发生可识别的MEFV突变而发生家族性地中海热而未接受秋水仙碱治疗。15岁那年，他被诊断患有免疫球蛋白（Ig）肾病，原因是存在大量蛋白尿和肾脏活检。下一代测序显示NM_001065.3：c.236C> T； m.236C> T。p。（Thr79Met）；TNFRFS1A中的T50M杂合子突变。用甲基泼尼松龙和环孢素治疗IgA肾病，然后用卡那基单抗治疗TRAPS。患者2，一名17岁的女性，在最近两个月内反复发作关节炎并伴有急性期反应物增加。她既没有发烧发作，也没有皮疹或肌痛。两次发作之间她的身体检查正常。膝盖和脚踝的磁共振成像均未显示出慢性关节炎的迹象。MEFV分析显示无突变。下一代测序揭示了NM_001065.3：c.362G> A； m.362G> A。p。（Arg121Gln）; TNFRFS1A中的R92Q杂合子突变。此后，用布洛芬成功治疗了关节炎发作。

总之，我们希望强调这两名患者在TNFRSF1A中具有不同序列变异的临床表现的多样性。此外，我们提出了TRAPS的罕见表现，即IgA肾病。