Abstract
Familial Mediterranean fever(FMF)is a hereditary autoinflammatory disease characterized by recurrent episodes of fever and serositis. It was inherited in an autosomal recessive mode caused by the MEFV gene, but it can also occur in heterozygotes and the presence of multiple variants of unknown significance(VUS). In addition, that mutation may modify the pathogenesis of other diseases. We report our experience with a family that presented with a variety of pathologies due to a combination of multiple MEFV variants. The cases are a 17-year-old male and a 15-year-old female sibling. Both were putative compound heterozygotes for pathogenic variant M694I(exon 10)and VUS E148Q(exon 2), with the older brother diagnosed typical FMF and the younger sister pre-symptomatic. In other relatives who have M694I, one diagnosed with protracted febrile myalgia syndrome(PFMS)and the others with autoinflammatory disease-like pathology that is atypical for FMF, suggesting clinical heterogeneity in the same family.
