Clinical and Genetic Features of Patients With TNFRSF1A Variants in Japan: Findings of a Nationwide Survey
Clinical and Genetic Features of Patients With TNFRSF1A Variants in Japan: Findings of a Nationwide Survey
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DOI：
10.1002/art.39793
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发表时间：
2016-11-01
影响因子：
13.3
通讯作者：
Horiuchi, Takahiko
中科院分区：
文献类型：
--
作者：
Ueda, Naoyasu;Ida, Hiroaki;Horiuchi, Takahiko
目的利用日本厚生劳动省肿瘤坏死因子受体相关周期性综合征（TRAPS）研究小组进行的全国性调查数据，阐明日本TNFRSF 1A变异体患者的临床和遗传特征。询问他们是否有疑似TRAPS的患者。对169名患者进行了TNFRSF 1A、MEFV和MVK基因检测。TNFRSF 1A变体的细胞表面表达进行了评估，使用293 T cells. Results 10例患者从10个独立的家庭被发现有TNFRSF 1A变体。我们收集了来自23个独立家族的另外41名TNFRSF 1A变异和炎症症状患者的临床和遗传信息;其中17名患者在文献中没有描述。日本患者的常见临床特征为发热>38 ℃（100%的患者）、关节痛（59%）和皮疹（55%）。日本患者中腹痛（36%）、肌痛（43%）和淀粉样变性（0%）的患病率显著低于白人患者。最常见的变异是T61 I（出现在49%的患者中），在363名健康对照中有7名被发现。半胱氨酸残基和T50 M变异缺陷与细胞表面表达减少，而其他变体，包括T61 I，是不是.ConclusionPatients与TNFRSF 1A的变体是非常罕见的，在日本，在其他国家，但有一些日本和高加索患者之间的临床和遗传差异。T61 I变异的致病意义尚不清楚。
ObjectiveTo elucidate the clinical and genetic features of patients with TNFRSF1A variants in Japan using data obtained from a nationwide survey conducted by the Ministry of Health, Labor, and Welfare of Japan study group for tumor necrosis factor receptor-associated periodic syndrome (TRAPS).MethodsInquiries were sent to 2,900 departments of internal medicine and pediatrics in all hospitals with more than 200 beds in Japan, asking whether they had patients in whom TRAPS was suspected. Genetic tests for TNFRSF1A, MEFV, and MVK were performed on 169 patients. Cell surface expression of TNFRSF1A variants was assessed using 293T cells.ResultsTen patients from 10 independent families were found to have TNFRSF1A variants. We collected clinical and genetic information on 41 additional patients with TNFRSF1A variants and symptoms of inflammation from 23 independent families; 17 of these patients had not been described in the literature. The common clinical features of Japanese patients were fever of >38 degrees C (100% of patients), arthralgia (59%), and rash (55%). The prevalence of abdominal pain (36%), myalgia (43%), and amyloidosis (0%) was significantly lower in Japanese patients than in Caucasian patients. The most common variant was T61I (appearing in 49% of patients), and it was identified in 7 of 363 healthy controls. Defects in cysteine residues and the T50M variant were associated with decreased cell surface expression, while other variants, including T61I, were not.ConclusionPatients with TNFRSF1A variants are very rare in Japan, as in other countries, but there are a number of clinical and genetic differences between Japanese and Caucasian patients. The pathogenic significance of the T61I variant remains unclear.