Journal Article

The Hereditary Periodic Fever Syndromes: Molecular Analysis of a New Family of Inflammatory Diseases

Michael Centola, Ivona Aksentijevich and Daniel L. Kastner

in Human Molecular Genetics

Volume 7, issue 10, pages 1581-1588
Published in print September 1998 | ISSN: 0964-6906
Published online September 1998 | e-ISSN: 1460-2083 | DOI:
The Hereditary Periodic Fever Syndromes: Molecular Analysis of a New Family of Inflammatory Diseases

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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.

Journal Article.  6622 words.  Illustrated.

Subjects: Genetics and Genomics

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