Patients with familial cold autoinflammatory syndrome (FCAS) suffer fever, urticaria and other conjunctivitis when exposed to cold air. Those with Muckle-Wells syndrome (MWS) frequently have sensorineural hearing loss and also suffer periodic fevers, but these bouts are unrelated to cold exposure. In 22 October on-line Nature Genetics Hal Hoffman and colleagues from University of California School of Medicine, San Diego identify a gene encoding an immune system protein implicated in these two rare disorders.

Hoffman et al. screened exons in a 10 cM region of chromosome 1q44 — to which FCAS and MWS have previously been mapped — for mutations using DNA from affected individuals and controls. They found four distinct mutations in a gene (called CIAS1) that segregated with the disorder. CIAS1 is expressed in peripheral blood leukocytes and encodes a newly found protein, named cryopyrin, with a structure that suggest a role in the regulation of inflammation...