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Fire and ice: An altered protein brings fever, chills

Scientists have identified the genetic basis of two rare disorders whose symptoms are apparently all caused by an altered immune system protein.

As reported by Hal M. Hoffman, M.D., and colleagues in todays online edition (the November print edition) of Nature Genetics, the protein, which they have named cryopyrin, is the likely culprit in two periodic fever syndromes: familial cold autoinflammatory syndrome (FCAS), in which affected people develop rashes and other symptoms when exposed to cold air, and Muckle-Wells syndrome (MWS), which causes deafness as well as periodic fevers.

Autoinflammatory conditions are those in which the body reacts as though it were being attacked by foreign organisms, despite the absence of such an attack.

Although these conditions are rare, they cause a considerable amount of misery. People with FCAS, for example, develop rash and flu-like symptoms, such as chills, fever and achy joints, when exposed to cool air, such as in air-conditioned rooms, says Dr. Hoffman, a grantee of the National Institute of Allergy and Infectious Diseases (NIAID).

The identification of the gene underlying FCAS and MWS not only helps researchers understand the origin of these rare conditions, but may also give direction to the search for causes and mechanisms at work in more common conditions.

As we begin to better understand cryopyrin, which evidently is a key regulatory protein, we are likely to learn more about such autoinflammatory diseases as Crohns disease, says Marshall Plaut, M.D., chief of NIAIDs Allergic Mechanisms Section.

Dr. Hoffman and his colleagues at the University of California, San Diego, analyzed the DNA of members of four families who have either FCAS or Muckle-Wells syndrome.

The researchers located four different mutations in the gene for cryopyrin. Each affected person studied had a mutation in this gene. In contrast, these mutations were not found in any unaffected family me
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Contact: Anne Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
22-Oct-2001


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