title: Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium.
abstract: Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by dramatic episodes of fever and serosal inflammation. This report describes the cloning of the gene likely to cause FMF from a 115-kb candidate interval on chromosome 16p. Three different missense mutations were identified in affected individuals, but not in normals. Haplotype and mutational analyses disclosed ancestral relationships among carrier chromosomes in populations that have been separated for centuries. The novel gene encodes a 3.7-kb transcript that is almost exclusively expressed in granulocytes. The predicted protein, pyrin, is a member of a family of nuclear factors homologous to the Ro52 autoantigen. The cloning of the FMF gene promises to shed light on the regulation of acute inflammatory responses.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000235:genetics*; D006238:Haploidy; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D011506:Proteins; D000070584:Tripartite Motif Proteins; C106984:TRIM38 protein, human; D044767:Ubiquitin-Protein Ligases