title: Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.
abstract: Familial cold autoinflammatory syndrome (FCAS, MIM 120100), commonly known as familial cold urticaria (FCU), is an autosomal-dominant systemic inflammatory disease characterized by intermittent episodes of rash, arthralgia, fever and conjunctivitis after generalized exposure to cold. FCAS was previously mapped to a 10-cM region on chromosome 1q44 (refs. 5,6). Muckle-Wells syndrome (MWS; MIM 191900), which also maps to chromosome 1q44, is an autosomal-dominant periodic fever syndrome with a similar phenotype except that symptoms are not precipitated by cold exposure and that sensorineural hearing loss is frequently also present. To identify the genes for FCAS and MWS, we screened exons in the 1q44 region for mutations by direct sequencing of genomic DNA from affected individuals and controls. This resulted in the identification of four distinct mutations in a gene that segregated with the disorder in three families with FCAS and one family with MWS. This gene, called CIAS1, is expressed in peripheral blood leukocytes and encodes a protein with a pyrin domain, a nucleotide-binding site (NBS, NACHT subfamily) domain and a leucine-rich repeat (LRR) motif region, suggesting a role in the regulation of inflammation and apoptosis.
authors.affiliation: Ludwig Institute for Cancer Research, University of California School of Medicine, San Diego, California, USA. hahoffman@ucsd.edu
authors.forename: H M
authors.initials: HM
authors.lastname: Hoffman
authors.forename: J L
authors.initials: JL
authors.lastname: Mueller
authors.forename: D H
authors.initials: DH
authors.lastname: Broide
authors.forename: A A
authors.initials: AA
authors.lastname: Wanderer
authors.forename: R D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D003080:Cold Temperature / Q000009:adverse effects*; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010375:Pedigree; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D000071198:Pyrin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D001798:Blood Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D011506:Proteins; D000071198:Pyrin; D012333:RNA, Messenger