A decision tree for genetic diagnosis of hereditary periodic fever in unselected patients
A decision tree for genetic diagnosis of hereditary periodic fever in unselected patients
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DOI：
10.1136/ard.2006.054304
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发表时间：
2006-11-01
影响因子：
27.4
通讯作者：
Touitou, I.
中科院分区：
文献类型：
--
作者：
Federici, L.;Rittore-Domingo, C.;Touitou, I.
背景：家族性地中海热(FMF)基因(地中海热(MEFV))分子分析的诊断价值仅在根据种族背景或临床标准选择的患者中得到证实。其他遗传性周期性发热综合征的基因诊断一直没有得到很好的评价。目的：在一大批未经选择的患者中，确定基因检测对遗传性周期性综合征的诊断贡献。方法：对1997-2005年间接受FMF基因检测的1941例患者进行回顾性研究。将MEFV基因分型与临床资料进行比较，评价FMF的诊断标准。对肿瘤坏死因子受体相关周期综合征(Traps)、高免疫球蛋白血症D综合征(HIDs)和低温比林相关周期综合征(CAPS)的基因检测也进行了综述。结果：在1574例有足够资料的患者中，71%的患者根据广泛使用的以色列标准进行了FMF的临床诊断。在这一亚组中只有409例患者(敏感度为37%)和15例(3.3%)临床诊断不太可能的FMF患者(特异度为97%)发现了两个MEFV突变。对456例FMF基因检测结果不确定的患者进行了交替遗传性周期性综合征的分子诊断。31例患者获得阳性诊断，包括TRAP(19例)、HIDS(4例)和CAPS(8例)。结论：对临床典型的FMF患者进行一线MEFV突变筛查可能只适用于特定地区。为了优化基因诊断，我们提出了一种决策树，在专家医生的建议下，它可以帮助将测试指征重新定向到非FMF遗传性周期性综合征。
Background: The diagnostic value of molecular analysis of the familial Mediterranean fever (FMF) gene (Mediterranean fever (MEFV)) has been well established only in patients selected on the basis of ethnic background or clinical criteria. Genetic diagnosis for other hereditary periodic fever syndromes has been poorly evaluated.Objective: To determine the diagnostic contribution of genetic tests for hereditary periodic syndromes in a large, unselected series of patients.Methods: A retrospective study was conducted on 1941 patients referred to us for FMF genetic tests between 1997 and 2005. MEFV genotypes were compared with clinical data to appraise criteria for FMF diagnosis. Genetic tests for tumour necrosis factor receptor-associated periodic syndrome (TRAPS), hyperimmunoglobulinaemia D syndrome (HIDS) and cryopyrin-associated periodic syndromes (CAPS) were also reviewed.Results: 71% of the 1574 patients with enough data had a clinical diagnosis of FMF according to the widely used Israeli criteria. Two MEFV mutations were found in only 409 patients of this subgroup (sensitivity = 37%) and in 15 (3.3%) of the patients with an improbable clinical diagnosis of FMF (specificity = 97%). Molecular diagnosis for alternate hereditary periodic syndromes was carried out in 456 of the patients having a non-conclusive FMF genetic test. A positive diagnosis was obtained in 31 of these patients (TRAPS (n = 19), HIDS (n = 4) and CAPS (n = 8)).Conclusions: First-line MEFV mutation screening in patients with clinically typical FMF may be appropriate only in particular areas. To optimise genetic diagnosis, we propose a decision tree, which, with the advice of an expert practitioner, could help redirect test indications towards non-FMF hereditary periodic syndromes.