A CANDIDATE GENE FOR FAMILIAL MEDITERRANEAN FEVER

Familiar Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and serositis. In this paper, we def ine a minimal co-segregating region of 60 kb containing the FMF gene ( MEFV) and identify four different transcript units within this region. One of these transcripts encodes a new protein (marenostrin) related to the ret-finger protein and to butyrophilin. Four conservative misse nse variations co-segregating with FMF have been found within the MEN candidate gene in 85% of the carrier chromosomes. These variations, wh ich cluster at the carboxy terminal domain of the protein, were not pr esent in 308 control chromosomes, including 162 validated non-carriers . We therefore propose that the sequence alterations in the marenostri n protein are responsible for the FMF disease.