title: Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts.
abstract: Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited diseases. They include three overlapping phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and urticarial skin rash are the main clinical features of these conditions. Renal amyloidosis and sensorineural complications may occur. Gain-of-function mutations in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a multimolecular complex involved in the inflammatory process. Missense mutations are almost always encountered, particularly in exon 3, which encodes the nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next-generation sequencing will grant access to new insights about NLRP3 implication in oligogenic and multifactorial diseases.
authors.affiliation: Laboratoire de génétique des maladies rares et auto-inflammatoires, CHRU, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sarrabay
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grandemange
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology; D009030:Mosaicism; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: CAPS; CINCA; FCAS; MWS; NLRP3; autoinflammatory syndrome; cryopyrin; inflammasome; mosaicism