Federici L, Rittore-Domingo C, Koné-Paut I, Jorgensen C, Rodière M, Le Quellec A, Touitou I
Laboratoire de Génétique, Hôpital A de Villeneuve, CHU de Montpellier, 34295 Montpellier Cedex 5, France.
Ann Rheum Dis. 2006 Nov;65(11):1427-32. doi: 10.1136/ard.2006.054304. Epub 2006 May 17.
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.
To determine the diagnostic contribution of genetic tests for hereditary periodic syndromes in a large, unselected series of patients.
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.
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)).
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.
家族性地中海热（FMF）基因（地中海热（MEFV））的分子分析诊断价值仅在基于种族背景或临床标准选择的患者中得到充分确立。其他遗传性周期性发热综合征的基因诊断评估不足。
确定在一大组未经选择的患者中，遗传性周期性综合征基因检测的诊断作用。
对1997年至2005年间转诊至我院进行FMF基因检测的1941例患者进行回顾性研究。将MEFV基因型与临床数据进行比较，以评估FMF诊断标准。还回顾了肿瘤坏死因子受体相关周期性综合征（TRAPS）、高免疫球蛋白D综合征（HIDS）和冷吡啉相关周期性综合征（CAPS）的基因检测。
在1574例有足够数据的患者中，71%根据广泛使用的以色列标准临床诊断为FMF。在该亚组的仅409例患者中发现了两个MEFV突变（敏感性 = 37%），在临床诊断为FMF可能性不大的患者中有15例（3.3%）发现了突变（特异性 = 97%）。对FMF基因检测无定论的456例患者进行了其他遗传性周期性综合征的分子诊断。其中31例患者得到阳性诊断（TRAPS（n = 19）、HIDS（n = 4）和CAPS（n = 8））。
临床典型FMF患者的一线MEFV突变筛查可能仅在特定地区适用。为了优化基因诊断，我们提出了一个决策树，在专家医生的建议下，它可以帮助将检测指征转向非FMF遗传性周期性综合征。
