title: Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes.
abstract: Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central-nervous-system involvement, and arthropathy. In the present study, we report, in seven unrelated patients with CINCA syndrome, distinct missense mutations within the nucleotide-binding site of CIAS1, a gene encoding cryopyrin and previously shown to cause Muckle-Wells syndrome and familial cold urticaria. Because of the severe cartilage overgrowth observed in some patients with CINCA syndrome and the implications of polymorphonuclear cell infiltration in the cutaneous and neurological manifestations of this syndrome, the tissue-specific expression of CIAS1 was evaluated. A high level of expression of CIAS1 was found to be restricted to polymorphonuclear cells and chondrocytes. These findings demonstrate that CIAS1 missense mutations can result in distinct phenotypes with only a few overlapping symptoms and suggest that this gene may function as a potential inducer of apoptosis.
authors.affiliation: Unité de Recherche sur le Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Feldmann
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Prieur
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.forename: Patrick
authors.initials: P
authors.lastname: Berquin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Certain
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cortis
authors.forename: Dominique
authors.initials: D
authors.lastname: Teillac-Hamel
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Genevieve
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D000595:Amino Acid Sequence; D001168:Arthritis / Q000151:congenital / Q000235:genetics*; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D019902:Chondrocytes / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000151:congenital / Q000235:genetics*; D008297:Male; D008581:Meningitis / Q000151:congenital / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000378:metabolism; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012871:Skin Diseases / Q000235:genetics*; D013577:Syndrome
chemical_list: D001798:Blood Proteins; D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012333:RNA, Messenger