The significance of paired MEFV mutations in individuals without symptoms of familial Mediterranean fever

The majority of patients with familial Mediterranean fever (FMF) have identifiable mutations in both alleles of the MEFV gene, while some individuals with paired MEFV mutations do not have clinical symptoms of the disease. During family studies we identified nine such individuals from six kindreds, most of whom either subsequently developed FMF or had other clinically significant inflammatory disease; one case benefiting substantially from colchicine therapy. Four individuals remained asymptomatic. Two further asymptomatic subjects with paired MEFV mutations were identified among 49 healthy controls from western Turkey, of whom a further 18.4 per cent were simple heterozygotes. This carrier rate was higher than would be expected from prevalence of FMF in this region, suggesting that penetrance of paired recognised pathogenic MEFV mutations may frequently be incomplete. MEFV genotyping results must be interpreted with due caution, and follow-up of apparently asymptomatic subjects with paired mutations is advisable