Objectives: The aim of the study is to explore the frequency of MEFV gene mutations in Egyptian patients with systemic onset juvenile idiopathic arthritis (SoJIA) and to investigate possible clinical significance of MEFV mutations.Methods: The study included 54 Egyptian children with systemic onset juvenile idiopathic arthritis(SOJIA), diagnosed according to the ILAR criteria for classification of JIA , all following up at pediatric rheumatology clinic, Abo ElReesh Hospital, Cairo University from 2004 to 2013, together with 30 age and gender matched healthy controls. All recruited children were screened for 12 common MEFV gene mutations using a reverse hybridization assay of biotinylated PCR products.Results: The study showed that SoJIA patients had a significantly higher frequency of MEFV mutations 36 cases (66.7%), compared with the healthy control population (10.%). V726A was the leading mutation, in SoJIA patients, with an allelic frequency of 15.74%, followed by E148Q with an allelic frequency of 7.4%. E148Q was the leading mutation, present in 13.3% of healthy controls.Conclusion: These findings suggest that mutations of the MEFV gene may be responsible for auto-inflammatory diseases, other than FMF, and patients with SoJIA especially ANA negatives, should be screened for MEFV gene mutations in countries where FMF is frequent.