PYRIN MARENOSTRIN MUTATIONS IN FAMILIAL MEDITERRANEAN FEVER/

Familial Mediterranean fever (FMF) is an inherited inflammatory diseas e that is frequently complicated by reactive systemic (AA) amyloidosis . It is principally recognized in certain Mediterranean populations, a nd the diagnosis depends on clinical features. Four mutations strongly linked to FMF have lately been identified in a gene encoding a novel protein that has been named pyrin or marenostrin. We studied 27 consec utive patients of varied ethnic origin, including an English man, who had classical, probable or possible FMF. Pyrin/marenostrin genotypes w ere determined, and AA amyloidosis was sought using serum amyloid P co mponent scintigraphy. Among the 23 patients with classical or probable FMF, 17 were homozygotes or compound heterozygotes for pyrin/marenost rin mutations, and in five, only single allele mutations were identifi ed. Two new mutations, T681I and Delta M694, were discovered in additi on to the four described previously. No mutations were identified in t hree of the four patients with possible FMF. Nine patients had AA amyl oidosis, but this association was not restricted to any particular gen otype. Most patients with FMF have mutations in both pyrin/marenostrin alleles, and genotyping at this locus is a valuable diagnostic test. Unidentified second mutations are likely to occur in FMF patients who have apparently solitary mutations, and therefore genotype results mus t be interpreted in conjunction with the clinical picture.