Dumont Anaël, Vergneault Hélène, Ardois Samuel, Boursier Guilaine, Lacout Carole, Aknouche Zohra, Aouba Achille, Cuisset Laurence, Grateau Gilles, Savey Léa, Georgin-Lavialle Sophie
Sorbonne University, Department of Internal Medicine, Tenon Hospital, AP-HP, Paris, France; Department of Internal Medicine, Caen University Hospital, Caen, France.
Sorbonne University, Department of Internal Medicine, Tenon Hospital, AP-HP, Paris, France; French National Reference Center for Autoinflammatory Diseases (CEREMAIA), Paris, France.
Joint Bone Spine. 2025 Jul;92(4):105850. doi: 10.1016/j.jbspin.2025.105850. Epub 2025 Jan 30.
To describe the main features and outcomes of a large cohort of adult familial Mediterranean fever (FMF) patients with one pathogenic MEFV mutations and compare them to FMF patients displaying 2 pathogenic MEFV mutations.
In a retrospective single-referential French center cohort of 581 patients with FMF, 178 FMF patients with one pathogenic mutation were retrieved and compared to 403 patients with 2 pathogenic MEFV mutations. The diagnosis of FMF was based on the Eurofever/PRINTO classification criteria for all patients, and they had all been sequenced for MEFV. Patients with M694V/E148Q genotype were also compared to M694V/WT patients.
Compared to FMF patients with 2 pathogenic MEFV mutations, patients with one pathogenic mutation showed significantly higher age at diagnosis and at disease onset (25 vs 10years and 12 vs 5years, P<0.001, respectively), higher personal history (21% vs 5%, P<0.001) or familial history (13% vs 5%, P=0.001) of recurrent aphthous stomatitis (RAS) and higher body mass index (BMI) (24 vs 23kg/m, P<0.05). Conversely, patients with one mutation showed no AA amyloidosis (0 vs 6%, P=0.001) and lower colchicine dosage (P<0.001) than patients with two pathogenic MEFV mutations. These differences remained significant after adjustments for age at disease onset (beginning in childhood or adulthood). No clinical difference was found between patients with M694V/E148Q and M694V/WT.
Adult FMF patients with a single pathogenic MEFV mutation display specific clinical features as well as different evolution compared to patients with 2 pathogenic MEFV mutations.
描述一大群携带一种致病性MEFV突变的成年家族性地中海热（FMF）患者的主要特征和结局，并将其与显示两种致病性MEFV突变的FMF患者进行比较。
在法国一个单中心的581例FMF患者的回顾性队列中，检索出178例携带一种致病性突变的FMF患者，并与403例携带两种致病性MEFV突变的患者进行比较。所有患者的FMF诊断均基于欧洲发热/PRINTO分类标准，且均对MEFV进行了测序。还将M694V/E148Q基因型患者与M694V/WT患者进行了比较。
与携带两种致病性MEFV突变的FMF患者相比，携带一种致病性突变的患者诊断时和疾病发作时的年龄显著更高（分别为25岁对10岁和12岁对5岁，P<0.001），复发性阿弗他口炎（RAS）的个人史（21%对5%，P<0.001）或家族史（13%对5%，P=0.001）更高，体重指数（BMI）也更高（24对23kg/m²，P<0.05）。相反，与携带两种致病性MEFV突变的患者相比，携带一种突变的患者没有AA淀粉样变性（0对6%，P=0.001）且秋水仙碱剂量更低（P<0.001）。在对疾病发作年龄（儿童期或成年期开始）进行调整后，这些差异仍然显著。M694V/E148Q患者与M694V/WT患者之间未发现临床差异。
与携带两种致病性MEFV突变的患者相比，携带单一致病性MEFV突变的成年FMF患者表现出特定的临床特征以及不同的病情发展。
