title: Genetic and clinical features of cryopyrin-associated periodic syndromes in Turkish children.
abstract: The aim of this study was to present the genetic and clinical data of the largest cohort of Turkish cryopyrin-associated periodic syndromes (CAPS) patients.
  
  
  
  This is a two-centre descriptive study of Turkish children with clinical diagnosis of CAPS. NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. ASC dependent NF-κB activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. Disease activity and response to anti interleukin 1 (anti-IL-1) treatment was also assessed.
  
  
  
  Heterozygous germline NLRP3 mutation was detected in 8 of 14 enrolled patients (57.1%). Two novel somatic mutations Y560H and G307D were found which induced both THP-1 cell death and ASC dependent NF-kB activation. With anti-IL-1 treatment the disease activity was improved in all patients except one. Except two patients with macrophage activation syndrome (MAS) attack, there were no serious adverse events requiring hospitalisation.
  
  
  
  CAPS should be considered in all patients with typical symptoms even if Sanger-based genetic analysis is negative, since a considerable number of patients have mosaicism. Treatment should be patient-tailored and MAS should be considered as a rare complication.
authors.affiliation: Hacettepe University Faculty of Medicine, Paediatric Nephrology-Rheumatology, Ankara, Turkey.
authors.forename: Fehime Kara
authors.initials: FK
authors.lastname: Eroglu
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Paediatric Rheumatology, Istanbul, Turkey.
authors.forename: Ozgür
authors.initials: O
authors.lastname: Kasapcopur
authors.affiliation: Hacettepe University Faculty of Medicine, Paediatric Nephrology-Rheumatology, Ankara, Turkey.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Beşbaş
authors.affiliation: Hacettepe University Faculty of Medicine, Paediatric Nephrology-Rheumatology, Ankara, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.affiliation: Hacettepe University Faculty of Medicine, Paediatric Nephrology-Rheumatology, Ankara, Turkey.
authors.forename: Yelda
authors.initials: Y
authors.lastname: Bilginer
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Paediatric Rheumatology, Istanbul, Turkey.
authors.forename: Kenan
authors.initials: K
authors.lastname: Barut
authors.affiliation: Hospital Clinic, Department of Immunology, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Mensa-Vilaro
authors.affiliation: Kyoto University Graduate School of Medicine, Department of Paediatrics, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Kyoto University Graduate School of Medicine, Department of Paediatrics, Kyoto, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.affiliation: Kyoto University Graduate School of Medicine, Department of Paediatrics, Kyoto, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.affiliation: Hospital Clinic, Department of Immunology, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Arostegui
authors.affiliation: Hacettepe University Faculty of Medicine, Paediatric Nephrology-Rheumatology, Ankara, Turkey. sezaozen@hacettepe.edu.tr.
authors.forename: Seza
authors.initials: S
authors.lastname: Ozen
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D053468:CARD Signaling Adaptor Proteins; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D055501:Macrophage Activation Syndrome / Q000235:genetics; D008297:Male; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012307:Risk Factors; D014162:Transfection; D016896:Treatment Outcome; D014421:Turkey
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D005819:Genetic Markers; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; C541220:canakinumab