De Pieri Carlo, Vuch Josef, De Martino Eleonora, Bianco Anna M, Ronfani Luca, Athanasakis Emmanouil, Bortot Barbara, Crovella Sergio, Taddio Andrea, Severini Giovanni M, Tommasini Alberto
Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
University of Trieste, Trieste, Italy.
Pediatr Rheumatol Online J. 2015 Apr 10;13:11. doi: 10.1186/s12969-015-0006-z. eCollection 2015.
Periodic fever syndromes (PFS) are an emerging group of autoinflammatory disorders. Clinical overlap exists and multiple genetic analyses may be needed to assist diagnosis. We evaluated the diagnostic value of a 5-gene sequencing panel (5GP) in patients with undiagnosed PFS.
Simultaneous double strand Sanger sequencing of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12 genes was performed in 42 patients with unexplained PFS. Clinical features were correlated with genetic results.
None of 42 patients analyzed displayed a causative genotype. However, single or multiple genetic variants of uncertain significance were detected in 24 subjects. Only in 5 subjects a definite diagnosis was made by taking into account both genetic and clinical data (2 TRAPS syndrome; 2 FMF; 1 FCAS). Statistical analysis showed that patients carrying genetic variants in one or more of the five selected genes displayed a significantly lower response to glucocorticoids compared with subjects who had completely negative genetic results.
The sequencing of multiple genes is of little help in the diagnostics of PFS and can often lead to results of uncertain interpretation, thus the clinically driven sequencing of single genes should remain the recommended approach. However, the presence of single or multiple genetic variants of uncertain significance, even if not allowing any specific diagnosis, correlated with a poorer response to glucocorticoids, possibly indicating a multifactorial subgroup of PFS with differential response to pharmacological treatment.
周期性发热综合征（PFS）是一组新出现的自身炎症性疾病。存在临床重叠情况，可能需要进行多项基因分析以辅助诊断。我们评估了一个5基因测序 panel（5GP）在未确诊的PFS患者中的诊断价值。
对42例不明原因的PFS患者进行MEFV、MVK、TNFRSF1A、NLRP3、NLRP12基因的双链桑格测序。将临床特征与基因结果相关联。
42例分析患者中均未显示出致病基因型。然而，在24名受试者中检测到了单个或多个意义未明的基因变异。仅在5名受试者中，通过综合考虑基因和临床数据做出了明确诊断（2例肿瘤坏死因子受体相关周期性综合征；2例家族性地中海热；1例家族性寒冷性自身炎症综合征）。统计分析表明，与基因结果完全阴性的受试者相比，在五个选定基因中的一个或多个基因中携带基因变异的患者对糖皮质激素的反应明显较低。
多个基因的测序对PFS的诊断帮助不大，且常常导致解释结果不确定，因此临床驱动的单个基因测序仍应是推荐的方法。然而，存在单个或多个意义未明的基因变异，即使不允许做出任何特定诊断，也与对糖皮质激素的反应较差相关，这可能表明PFS存在一个对药物治疗反应不同的多因素亚组。
Zotero 插件
