Ben-Chetrit E, Urieli-Shoval S, Calko S, Abeliovich D, Matzner Y
Department of Medicine, Hadassah University Hospital in Ein Kerem, Jerusalem, Israel.
Clin Exp Rheumatol. 2002 Jul-Aug;20(4 Suppl 26):S25-9.
Traditionally, the diagnosis of familial Mediterranean fever (FMF) has been based on clinical manifestations and the physician's experience. Following the cloning of the gene associated with this disease (MEFV), genetic analysis of its mutations has become available, providing a new tool for the establishment or confirmation of the diagnosis of FMF.
We analyzed the results of molecular testing for MEFV mutations in 600 individuals. We wished to determine how many of them bore mutations and what percentage had clinically active FMF. We also compared the rate of genetic confirmation of the FMF diagnosis in referrals with suspected FMF seen by general practitioners with that of persons sent for genetic analysis by FMF experts.
Of 600 individuals tested for FMF mutations, we analyzed separately 446 unrelated persons for the combination of their mutations, epidemiological data, and clinical manifestations. The five most common mutations in the present cohort were analyzed using the amplification refractory mutation system (ARMS).
Of the 446 subjects analyzed, 249 (55%) bore mutations: 147 of these were homozygotes or compound heterozygotes, all of whom had FMF according to clinical criteria. Of the remaining 102 heterozygotes, 72 had FMF according to clinical criteria. Two patients with none of the five mutations also had FMF: North African Jews bore mainly mutations M694V and E148Q. The M6941 mutation was found exclusively in Palestinian Arabs. The rate of confirmation of FMF diagnosis by mutation analysis in subjects sent by FMF experts was significantly higher than that of persons referred by general practitioners. Analysis of the molecular testing of the multicase families (154 individuals) revealed that 141 of them bore MEFV mutations and that 4 persons homozygous for E148Q were asymptomatic.
Molecular analysis of FMF mutations confirmed the diagnosis in about 60% of the referrals with suspected FMF. Some (33%) of the patients were heterozygotes, and there were also FMF patients with none of the 5 mutations analyzed. A second opinion by an FMF expert may decrease the need for mutation analysis in subjects suspected of having FMF.
传统上，家族性地中海热（FMF）的诊断基于临床表现和医生的经验。在克隆出与该疾病相关的基因（MEFV）之后，对其突变进行基因分析成为可能，为FMF诊断的确立或确认提供了一种新工具。
我们分析了600例个体MEFV突变的分子检测结果。我们希望确定其中有多少人携带突变以及有临床活动型FMF的比例是多少。我们还比较了全科医生转诊的疑似FMF患者与FMF专家送去进行基因分析的患者中FMF诊断的基因确认率。
在检测FMF突变的600例个体中，我们分别分析了446例无亲缘关系个体的突变组合、流行病学数据和临床表现。使用扩增阻滞突变系统（ARMS）分析了本队列中最常见的5种突变。
在分析的446例受试者中，249例（55%）携带突变：其中147例为纯合子或复合杂合子，根据临床标准，所有这些人都患有FMF。其余102例杂合子中，72例根据临床标准患有FMF。2例无这5种突变的患者也患有FMF：北非犹太人主要携带M694V和E148Q突变。M694I突变仅在巴勒斯坦阿拉伯人中发现。FMF专家送去检测的受试者中通过突变分析确认FMF诊断的比例显著高于全科医生转诊的患者。对多病例家族（154例个体）的分子检测分析显示，其中141例携带MEFV突变，4例E148Q纯合子无症状。
FMF突变的分子分析在约60%的疑似FMF转诊患者中确认了诊断。一些患者（33%）为杂合子，也有未检测到所分析的5种突变的FMF患者。FMF专家的二次诊断可能会减少疑似FMF患者进行突变分析的需求。
