- Paper Report
- Open Access
Mutations in CIAS1gene cause familial cold autoinflammatory syndrome and Muckle-Wells syndrome
- Roberto Caricchio1
© Biomed Central Ltd 2002
- Received: 16 January 2002
- Accepted: 17 January 2002
- Published: 17 January 2002
Autoinflammatory syndromes are rare conditions defined by recurrent inflammatory symptoms. Phenotype varies among these diseases; however a subgroup is characterized by intermittent attacks of fever associated with rash and arthralgia. These diseases include familial mediterranean fever (FMF), hyper-IgD syndrome (HIDS), TNF receptor-associated periodic syndrome (TRAPS), familial cold autoinflammatory syndrome (FCAS), and Muckle-Wells syndrome (MWS). Mutations in the MEFV gene in FMF, mevalonate kinase in HIDS, and TNFR1 in TRAPS have been previously identified. In this paper the authors described a new gene (CIAS1) in which mutations are found in FCAS and MWS.
Initial studies identified a locus for FCAS on chromosome 1q44. With expressed sequence tag (EST) mapping of this region, the authors identified missense mutations in exon 3 of the CIAS1 gene. Three families with FCAS and one with MWS were studied. Each family showed a unique missense mutation. These mutations were not found in unaffected members of the families or in controls. CIAS is expressed mainly, at a low level, in peripheral blood leukocytes; an expression pattern similar to the gene involved in FMF (MEFV). Moreover, analysis of genomic exon sequence revealed alternative splicing of exons 4-8. Analysis of the predicted protein (Cryopyrin) encoded by the first splice form of CIAS1identifield an N-terminal pyrin domain, a central NACHT domain, and a C-terminal LRR domain. The structural characteristics suggest that the protein is a signaling protein involved in the regulation of inflammation and apoptosis.
Gene mapping and cloning, missense mutation analysis, exon prediction programs, northern analysis.
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