A new low‐penetrance TNFRSF1A mutation causing atypical periodic fever
A new low‐penetrance TNFRSF1A mutation causing atypical periodic fever
复制标题
一种新的低外显率TNFRSF1A突变导致非典型周期性发热
作者：
A. Rack;S. Stojanov;B. Belohradsky;P. Lohse
通讯员：Peter Lohse，临床化学系- Grosshadern，慕尼黑大学，Marchioninistr.org。15，D - 81377慕尼黑，德国。电子邮件：peter. med.uni-muenchen.de Silvia Stojanov MD，国立卫生研究院，遗传学和基因组学分支，NIAMS，Building 9，Room 1 W111，9 Memorial Drive - MSC 0908，Bethesda，MD 20892 - 0908，USA * 本作品包含Anita Rack未发表的博士论文的部分内容。2004年6月11日收到; 2005年1月31日接受。遗传性周期性发热综合征由全身性炎症和反复发热发作定义。这种疾病的常染色体显性形式是肿瘤坏死因子（TNF）受体1相关周期性综合征（TRAPS）。1它是由染色体12 p13上的TNFRSF 1A基因突变引起的，该基因编码细胞表面55 kDa TNF受体（TNFR 1）。TNF与TNFR 1的结合导致受体三聚化和细胞内信号转导级联的激活。这种反应可以通过受体蛋白的酶诱导的蛋白水解切割（脱落）来修饰艾德。循环受体也结合TNF并通过与膜结合受体竞争影响炎症程度。TNFRSF 1A基因的突变被认为会改变受体胞外部分的构象，在某些情况下，这会导致脱落减少。在临床上，TRAPS的特征在于持续一至数周的发热发作、严重腹痛、离心性迁移性肉芽肿性皮肤病变、局部肌痛和伴有或不伴有眶周水肿的结膜炎。在疾病发作期间，中性粒细胞的数量、C-反应蛋白（CRP）水平和血清淀粉样蛋白A浓度通常升高，而可溶性1型TNF受体血清浓度可降低。表现的年龄介于婴儿期和生命的第二个十年之间。肾脏淀粉样变性和在少数情况下肝脏淀粉样变性是最严重的并发症，其极大地影响受影响个体的预后。患者报告
Correspondence: Peter Lohse, Department of Clinical Chemistry – Grosshadern, University of Munich, Marchioninistr. 15, D – 81377 Munich, Germany. Email: peter.lohse@med.uni-muenchen.de Present address: Silvia Stojanov MD, National Institutes of Health, Genetics and Genomics Branch, NIAMS, Building 9, Room 1W111, 9 Memorial Drive – MSC 0908, Bethesda, MD 20892 – 0908, USA * This work contains parts of the unpublished doctoral thesis of Anita Rack. Received 11 June 2004; accepted 31 January 2005. Hereditary periodic fever syndromes are defi ned by systemic infl ammation and recurrent fever episodes. An autosomal dominant form of this disease entity is the tumor necrosis factor (TNF) receptor 1-associated periodic syndrome (TRAPS). 1 It is caused by mutations in the TNFRSF1A gene on chromosome 12p13, encoding the cell-surface 55 kDa TNF receptor (TNFR1). Binding of TNF to TNFR1 results in receptor trimerization and activation of intracellular signal transduction cascades. This response can be modifi ed by enzyme-induced proteolytic cleavage (shedding) of the receptor protein. The circulating receptors also bind TNF and infl uence the degree of infl ammation by competing with membrane-bound receptors. Mutations in the TNFRSF1A gene are believed to change the conformation of the extracellular part of the receptor, which, in some instances, leads to reduced shedding. Clinically, TRAPS is characterized by fever episodes of one to several weeks duration, severe abdominal pain, centrifugally migrating erythematous skin lesions, localized myalgia, and conjunctivitis with or without periorbital edema. During the disease episodes, the number of neutrophils, the C-reactive protein (CRP) levels, and the serum amyloid A concentrations are usually elevated, while the soluble type 1 TNF receptor serum concentration can be reduced. The age of manifestation lies between infancy and the second decade of life. Amyloidosis of the kidneys and, in fewer cases, of the liver is the most severe complication which greatly infl uences the prognosis of affected individuals. Patient report