title: The hereditary periodic fever syndromes: molecular analysis of a new family of inflammatory diseases.
abstract: The hereditary periodic fever syndromes are a group of Mendelian disorders characterized by episodic fever and serosal or synovial inflammation. Familial Mediterranean fever (FMF) and the hyperimmunoglobulinemia D and periodic fever syndrome are both recessively inherited, while three dominantly inherited syndromes have been described, the best-characterized of which is familial Hibernian fever (FHF). The last year has seen two major developments in this field: the FMF gene was identified on chromosome 16p by positional cloning, and a second major periodic fever locus was mapped to distal chromosome 12p. The FMF gene (MEFV) encodes a novel 781 amino acid protein; to date, eight different missense mutations and a number of polymorphisms have been described. Seven of the eight mutations occur within a region of 82 amino acids near the C-terminus. Computational analysis of the conceptual protein reveals five different domains/motifs compatible with a nuclear effector function. MEFV is expressed preferentially in granulocytes and myeloid bone marrow precursors, giving rise to speculation that the protein may serve as a transcriptional regulator of inflammation in granulocytes. The second periodic fever locus was mapped by two different groups: one studying FHF, the other studying a similar dominantly inherited syndrome designated familial periodic fever. Both genes map to the same 19 cM region on distal chromosome 12p, strongly suggesting a common locus. The molecular characterization of the periodic fever genes should provide important new insights into the regulation of inflammation in general.
authors.affiliation: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Building 10, Room 9N210, 9000 Rockville Pike, Bethesda, MD 20892-1820, USA.
authors.forename: M
authors.initials: M
authors.lastname: Centola
authors.forename: I
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: D L
authors.initials: DL
authors.lastname: Kastner
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005334:Fever / Q000235:genetics*; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D000071198:Pyrin; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin