title: Clinical and genetic characterization of Italian patients affected by CINCA syndrome.
abstract: OBJECTIVE
  We report the experience of the Italian Registry of patients affected by chronic infantile neurological, cutaneous, articular (CINCA) syndrome. The clinical and genetic features of 12 unrelated Italian patients with CINCA syndrome are described, focusing on the possible influence of the presence of CIAS1/cryopyrin mutations on the phenotype of the disease and on its prognosis.
  
  
  METHODS
  The clinical features of 12 Italian CINCA patients were evaluated. Genomic DNA of the patients was sequenced using specific primers for CIAS1 and ASC genes.
  
  
  RESULTS
  Our patients shared typical CINCA characteristics and, sometimes, remarkable perinatal events, peculiar of CIAS1-mutated patients. Seven patients carried CIAS1 missense mutation, localized within the nucleotide binding domain of cryopyrin. Four previously described mutations and three new heterozygous CIAS1 missense mutations were identified. ASC gene, encoding for a direct interactor of cryopyrin, was not mutated in Italian CINCA patients. Finally, we reported the efficacy and safety of anti-IL1 therapy (Anakinra) in seven patients with a particularly severe CINCA phenotype.
  
  
  CONCLUSIONS
  Despite some common signs-used as syndrome hallmarks-we observed a high variability in symptoms, genetic results and outcomes in Italian CINCA patients. In contrast with other authors, we cannot find out any correlation between mutations in CIAS1 and CINCA severity, but we underlined the concomitance of perinatal events and mental retardation only in CIAS1 mutated subjects. Finally, we confirmed the efficacy of Anakinra treatment, both in CIAS1-mutated and non-mutated patients.
authors.affiliation: Department of Molecular Genetics, IRCCS G. Gaslini, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Caroli
authors.forename: A
authors.initials: A
authors.lastname: Pontillo
authors.forename: A
authors.initials: A
authors.lastname: D'Osualdo
authors.forename: L
authors.initials: L
authors.lastname: Travan
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: S
authors.initials: S
authors.lastname: Crovella
authors.forename: M
authors.initials: M
authors.lastname: Alessio
authors.forename: A
authors.initials: A
authors.lastname: Stabile
authors.forename: M
authors.initials: M
authors.lastname: Gattorno
authors.forename: A
authors.initials: A
authors.lastname: Tommasini
authors.forename: A
authors.initials: A
authors.lastname: Martini
authors.forename: L
authors.initials: L
authors.lastname: Lepore
mesh_terms: D000293:Adolescent; D000328:Adult; D001168:Arthritis / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008297:Male; D020125:Mutation, Missense; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012042:Registries; D013577:Syndrome; D016896:Treatment Outcome; D014581:Urticaria / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human