Rheumatology Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
CEREMAIA, Department of Genetics, CHU of Montpellier, INSERM, University of Montpellier, Montpellier, France.
Clin Genet. 2024 Sep;106(3):217-223. doi: 10.1111/cge.14566. Epub 2024 May 31.
Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever, serositis (peritonitis, pleuritis, or synovitis), and erysipelas-like erythema. Genetic variants in the MEFV gene are associated with this disease. Familial Mediterranean fever is considered an autosomal recessive disease. However, in Middle Eastern countries, a third of the patients expressing FMF manifestations, carry a single mutation only. Moreover, some cases of pure dominant inheritance linked to specific single MEFV variants have also been described. This complex inheritance of MEFV-associated inflammatory diseases poses a serious challenge when interpreting the results of genetic testing in patients having recurrent fever syndromes. In addition, in certain situations, asymptomatic individuals may be incidentally found to carry MEFV variants. These cases pose the question of their exact diagnosis and whether they should be treated. Previous studies have focused on genetic results interpretations among symptomatic patients. In the current article, we would like to elaborate on the genetic interpretation in cases of symptomatic individuals suspected to have FMF and on asymptomatic individuals carrying MEFV variants. We aim to assist physicians unfamiliar with FMF to cope with genetic results interpretation when facing symptomatic and asymptomatic individuals carrying MEFV variants and suggest a management plan accordingly.
家族性地中海热（FMF）是一种自身炎症性疾病，其特征为反复发作的发热、浆膜炎（腹膜炎、胸膜炎或滑膜炎）和丹毒样红斑。MEFV 基因的遗传变异与这种疾病有关。家族性地中海热被认为是一种常染色体隐性疾病。然而，在中东国家，三分之一表现出 FMF 特征的患者仅携带单个突变。此外，还描述了一些与特定的单一 MEFV 变异相关的纯显性遗传病例。MEFV 相关炎症性疾病的这种复杂遗传给具有复发性发热综合征的患者的基因检测结果解释带来了严重挑战。此外，在某些情况下，无症状个体可能偶然携带 MEFV 变异。这些情况提出了他们的确切诊断问题以及是否应该治疗的问题。以前的研究主要集中在有症状患者的遗传结果解释上。在本文中，我们希望详细阐述疑似 FMF 的有症状个体和携带 MEFV 变异的无症状个体的遗传解释。我们的目的是帮助不熟悉 FMF 的医生在面对携带 MEFV 变异的有症状和无症状个体时应对遗传结果解释，并提出相应的管理计划。
