title: CARD15 mutations are rare in Swedish pediatric Crohn disease.
abstract: BACKGROUND
  An association between mutations in a gene involved in bacterial recognition by monocytes, CARD15/NOD2 and Crohn disease (CD) has been reported in studies of adults and children. The aim of this study was to investigate the presence of CARD15 mutations in Swedish children with CD and analyze genotype-phenotype correlations.
  
  
  METHODS
  Fifty-eight children (62% boys) with CD diagnosed between 2.8 and 16.9 years (median 10.9 years), were reviewed. Histopathology, retrospective data collection and mutational analyses for the three main mutations R702W, G908R and 1007fs were independently performed. First-degree relatives were also genotyped.
  
  
  RESULTS
  A CARD15 mutation was found in 8.6% (95% confidence interval, 2.9% to 19.0%), all of whom were heterozygotes, giving an overall allele frequency of 4.3% (95% confidence interval, 1.4-9.8). In 12%, all patients without mutations, a first-degree relative had CD. In four of five children, mutations were transferred from their healthy mothers. Granulomas at onset were found in 80% of patients with mutations and in 43% of those without (P = 0.17). No statistical association was found between mutation and phenotype regarding age at onset, anatomic location at onset or follow-up, severity of inflammation at onset, development of stenosis, perianal disease or extra intestinal manifestations.
  
  
  CONCLUSIONS
  The frequency of CARD15 mutation in this Swedish pediatric CD population is lower than reported in a mixed adult and pediatric population. The genotype-phenotype correlations were non-significant although a trend was found between the presence of mutations and granuloma formation. Healthy heterozygote mothers conveyed the mutation to their children with CD.
authors.affiliation: Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. maja.idestrom@karolinska.se
authors.forename: Maja
authors.initials: M
authors.lastname: Ideström
authors.forename: Carlos
authors.initials: C
authors.lastname: Rubio
authors.forename: Fredrik
authors.initials: F
authors.lastname: Granath
authors.forename: Yigael
authors.initials: Y
authors.lastname: Finkel
authors.forename: J-P
authors.initials: JP
authors.lastname: Hugot
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013548:Sweden
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein