title: NOD2/CARD15 gene mutations in patients with familial Mediterranean fever.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) and Crohn's disease are autoinflammatory disorders, associated with genes (MEFV and NOD2/CARD15, respectively) encoding for regulatory proteins, important in innate immunity, apoptosis, cytokine processing, and inflammation. Although mutations in the MEFV gene were shown to modify Crohn's disease, the role of NOD2/CARD15 gene mutations in the FMF disease phenotype was never studied before.
  
  
  METHODS
  The cohort consisted of 103 consecutive children with FMF, followed in a single referral center. NOD2/CARD15 genotypes were analyzed in all patients and 299 ethnically matched unaffected controls. Demographic data, clinical characteristics, and disease course of FMF patients with and without NOD2/CARD15 mutation were compared.
  
  
  RESULTS
  A single NOD2/CARD15 mutation was detected in 10 (9.7%) FMF patients and 26 (8.7%) controls. No homozygous or compound heterozygous subjects were discovered in the 2 groups. FMF patients carrying a NOD2/CARD15 mutation had a higher rate of erysipelas-like erythema and acute scrotum attacks, a trend for a higher rate of colchicine resistance and a more severe disease as compared with patients without mutations.
  
  
  CONCLUSIONS
  NOD2/CARD15 mutations are not associated with an increased susceptibility to develop FMF. Nevertheless, the presence of these mutations in FMF patients appears to be associated with a trend to a more severe disease.
authors.affiliation: Department of Pediatrics and Pediatric Rheumatology, Hadassah Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel. berkun@post.tau.ac.il
authors.forename: Yackov
authors.initials: Y
authors.lastname: Berkun
authors.forename: Amir
authors.initials: A
authors.lastname: Karban
authors.forename: Shai
authors.initials: S
authors.lastname: Padeh
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.forename: Yael
authors.initials: Y
authors.lastname: Shinar
authors.forename: Merav
authors.initials: M
authors.lastname: Lidar
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bujanover
mesh_terms: D000208:Acute Disease; D002675:Child, Preschool; D015331:Cohort Studies; D003078:Colchicine / Q000627:therapeutic use; D004351:Drug Resistance; D004890:Erythema / Q000209:etiology / Q000473:pathology; D010505:Familial Mediterranean Fever / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011379:Prognosis; D012611:Scrotum / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D003078:Colchicine