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Objectives: Certain genetic variants in the CARD15 gene are accompanied by an enhanced risk to develop Crohn disease with the main activity in the terminal ileum and ensuing stricturing early in life. The objective of this study was to evaluate the relation between CARD15 mutations and overall disease activity and response to therapy in pediatric patients.Methods: 65 genomic DNA samples from such patients were tested for the presence of three main Crohn associated mutations in CARD15 by direct genomic sequencing. The number of mutations (none, one or two alleles affected) was correlated with body mass index and height, Pediatric Crohn Disease Activity Index, therapy and therapeutical success in terms of body mass index and Pediatric Crohn Disease Activity Index improvement.Results: The authors found a nonsignificant trend of a lower body mass index and higher Pediatric Crohn Disease Activity Index in patients with CARD15 mutations. Physicians uninformed about their CARD15 status prescribed significantly more budesonide and prednisolone intermittently and more alimentary supplementation to these patients. The average improvement in terms of body mass index and Pediatric Crohn Disease Activity Index after 2 years of therapy was roughly similar in all patient groups.Conclusions: Pediatric Crohn patients with CARD15 mutations have a higher disease activity and need a more intensive therapy. With some exceptions, their medium-term response to therapy is nevertheless satisfying. [ABSTRACT FROM AUTHOR]

Objectives: Crohn disease is a chronic inflammatory bowel disorder that is caused by environmental and genetic factors. Mutations in the CARD15 gene have been recently identified to be associated with the disease. Until now no genetic study has focused directly on a pediatric population.Methods: The authors sequenced all 12 exons of the CARD15 gene in 55 pediatric patients with Crohn disease from Saxony. Their average age at onset was 11.2 years (1-17.5 years). The authors also evaluated the genotype-phenotype relationship in the patients.Results: Fourteen different polymorphic and/or disease-related nucleotide alterations have been identified in the patients. Sixty-five percent of their genomic DNA samples harbored at least one of six mutations within the CARD15 gene, which previously has been identified as being associated with Crohn disease. The authors found that the cytosine insertion mutation 3020insC was significantly more common in their pediatric population than in patients with Crohn disease (26% versus 11% of the alleles) whose results were reported in the literature. The genotype-phenotype analysis showed that the authors' patients with at least one of the six CARD15 disease-associated mutations had a high risk of inflammation located in the terminal ileum and ascending colon. In 10 of 19 patients with two mutations, intestinal resection surgery was necessary because of stricturing.Conclusions: In the authors' pediatric patients, the genetic influence on Crohn disease was more pronounced than that reported in any other study, and it strongly affected the clinical phenotype. [ABSTRACT FROM AUTHOR]