Impact of MEFV gene variants on clinical presentation in Familial Mediterranean Fever: A focus on Exon 2 mutations Impacto de las variantes del gen MEFV en la presentación clínica de la fiebre mediterránea familiar: enfoque en las mutaciones del exón 2

Kulaksiz B., Acar B., Kizilkaya O. O., Aktas B., UĞURLU S.

Reumatologia Clinica, cilt.22, sa.1, 2026 (ESCI, Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.reuma.2025.502040
  • Dergi Adı: Reumatologia Clinica
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, EMBASE, MEDLINE, DIALNET
  • Anahtar Kelimeler: E148Q, Exon 2, Familial Mediterranean Fever, M694V, MEFV gene, R202Q
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Aim: Our study aimed to evaluate the clinical presentation, demographics and colchicine response in Familial Mediterranean Fever (FMF) patients with Exon 2 mutations (E148Q, R202Q) compared to those with Exon 10 mutations. Methods: A single-center retrospective study was conducted on 98 adult FMF patients diagnosed between 2009 and 2019. Medical records of 41 patients with Exon 2 and 57 patients with Exon 10 mutations were reviewed. In Exon 2 group, 3 patients were homozygous for E148Q, 33 were heterozygous (21 with E148Q, 12 with R202Q), and 5 were compound heterozygous for E148Q and R202Q. In the Exon 10 group, 20 patients were homozygous for M694V, 18 were heterozygous, and 19 had compound heterozygous mutations involving M694V and other Exon 10 variants (V726A, M680I, A744S, R761H). Data on demographics, symptom onset, clinical manifestations, family history, colchicine response were analyzed. Results: Patients with Exon 2 mutations were older at symptom onset (p < 0.001) and had fewer family histories (p < 0.001). Typical FMF symptoms like fever (p = 0.030) and abdominal pain (p = 0.018) were more common in Exon 10 patients. Conversely, musculoskeletal symptoms, including arthralgia (p = 0.004) and myalgia (p = 0.013), were more frequent in Exon 2 patients. Both groups had similar rates of amyloidosis (p = 1.0). Colchicine was effective in 91.7% of Exon 2 patients and 96.4% of Exon 10 patients (p = 0.376). Conclusion: Exon 2 mutations are associated with atypical presentations in FMF. Arthralgia and myalgia presentations are mostly indicative of Exon 2 variant, while a family history and earlier age of symptom onset are characteristic of Exon 10 variant. Clinicians should recognize the complex nature of FMF and adopt a personalized approach.