E148Q mutation: a disease-causing mutation or a sequence variant? Disease severity in specific ethnic groups of Familial Mediterranean Fever patients

Abstract Aim: Evaluate clinical characteristics and disease severity in specific ethnic groups of FMF patients homozygous for the E148Q mutation, and examine the contribution of a single allele V726A mutation to disease severity. Methods: A retrospective cohort study included patients homozygous for the E148Q mutation. The Characteristics of FMF patients with E148Q/E148Q and E148Q/E148Q + V726A/- MEFV mutations were compared. The primary outcome measure was FMF disease severity as measured by Tel Hashomer Key to Severity Score among patients homozygous for the E148Q mutation alone or with an additional V726A mutation. Results: A total of 61 FMF patients were included of which 24 (39%) had the E148Q/E148Q MEFV mutation and 37 (61%) had the E148Q/E148Q + V726A/- MEFV mutation. Patients with the E148Q/E148Q + V726A/- MEVF mutation were significantly more often of Druze descent compared to patients with the E148Q/E148Q MEFV mutation. Most patients had mild or moderate disease severity. CRP levels decreased significantly after colchicine treatment. Conclusion: Patients with the E148Q mutation alone present with mild to moderate disease severity in all ethnic groups of Israeli FMF patients. Disease severity did not differ between patients with E148Q/E148Q + V726A/- MEFV mutation and E148Q/E148Q mutation alone. Colchicine treatment should be given