The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome
The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome
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DOI：
10.1002/art.10429
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发表时间：
2002-08-01
影响因子：
--
通讯作者：
Grateau, G
中科院分区：
文献类型：
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作者：
Dodé, C;André, M;Grateau, G
objective.研究394例不同种族的复发性炎症综合征患者肿瘤坏死因子受体相关周期性综合征（TRAPS）的频率、临床症状和基因型特征。对128例高度怀疑TRAPS的患者进行TNFRSF1A基因编码区测序，并对266例无或仅有1个地中海热基因（MEFV）突变的复发性炎症综合征患者进行变性高效液相色谱系统筛查。在394例无关患者中，有28例（7.1%）发现TNFRSF1A突变。28例患者中有9例（32%）有复发性炎症综合征家族史。在13名患者中，炎症发作的时间少于5天。其中三个突变（Y20H、L67P和C96Y）是新的。两个突变，R92Q和（主要）P46L，分别在12和10例患者中发现，与其他突变相比，具有较低的突变率。TNFRSF1A突变在不同种族的患者中发现，包括那些有家族性地中海热（IMF）风险的人：亚美尼亚人，塞法迪犹太人，特别是来自马格里布的阿拉伯人。28例患者中仅3例（10.7%）有淀粉样变性。TRAPS是一种未被诊断的复发性炎症综合征的原因。它存在于地中海血统的人群中，并且炎症发作的持续时间短，这可能导致FMF的错误诊断。由于复发性炎症综合征患者的准确诊断对于适当的临床管理和治疗至关重要，因此需要进行TNFRSF1A的遗传筛查。
Objective. To characterize the frequency, clinical signs, and genotypic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a series of 394 patients of various ethnic origins who have recurrent inflammatory syndromes.Methods. Sequencing of the coding region of the TNFRSF1A gene was performed in 128 patients in whom there was a high suspicion of TRAPS, and denatured high-performance liquid chromatography was used to systematically screen for TNFRSF1A in 266 patients with recurrent inflammatory syndrome and no or only 1 Mediterranean fever gene (MEFV) mutation.Results. TNFRSF1A mutations were found in 28 (7.1%) of 394 unrelated patients. Nine (32%) of the 28 patients had a family history of recurrent inflammatory syndromes. In 13 patients, the length of the attack of inflammation was fewer than 5 days. Three of the mutations (Y20H, L67P, and C96Y) were novel. Two mutations, R92Q and (mainly) P46L, found in 12 and 10 patients, respectively, had lower penetrance compared with other mutations. TNFRSF1A mutations were found in patients of various ethnic origins, including those at risk for familial Mediterranean fever (IMF): Armenians, Sephardic Jews, and especially Arabs from Maghreb. Only 3 (10.7%) of the 28 patients had amyloidosis.Conclusion. TRAPS is an underdiagnosed cause of recurrent inflammatory syndrome. Its presence in the population of persons of Mediterranean ancestry and the short duration of the attacks of inflammation can lead to a fallacious diagnosis of FMF. Because an accurate diagnosis in patients with recurrent inflammatory syndromes is crucial for proper clinical management and treatment, genetic screening for TNFRSF1A is warranted.