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Targeted gene panel sequencing in children with very early onset inflammatory bowel disease—evaluation and prospective analysis
  1. Jochen Kammermeier1,2,
  2. Suzanne Drury3,
  3. Chela T James4,
  4. Robert Dziubak1,
  5. Louise Ocaka4,
  6. Mamoun Elawad1,
  7. Philip Beales2,
  8. Nicholas Lench3,
  9. Holm H Uhlig5,6,
  10. Chiara Bacchelli2,
  11. Neil Shah1,7
  1. 1Department of Gastroenterology, Great Ormond Street Hospital for Children, London, UK
  2. 2Experimental & Personalised Medicine Section, Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK
  3. 3North East Thames Regional Genetics Service, Hospital for Children, London, UK
  4. 4Centre for Translational Omics-GOSgene, Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK
  5. 5Translational Gastroenterology Unit, University of Oxford, Oxford, UK
  6. 6Department of Pediatrics, University of Oxford, Oxford, UK
  7. 7Katholic University Leuven, Leuven, Belgium
  1. Correspondence to Dr J Kammermeier, University College London (Institute of Child Health) and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK; j.kammermeier{at}


Background Multiple monogenetic conditions with partially overlapping phenotypes can present with inflammatory bowel disease (IBD)-like intestinal inflammation. With novel genotype-specific therapies emerging, establishing a molecular diagnosis is becoming increasingly important.

Design We have introduced targeted next-generation sequencing (NGS) technology as a prospective screening tool in children with very early onset IBD (VEOIBD). We evaluated the coverage of 40 VEOIBD genes in two separate cohorts undergoing targeted gene panel sequencing (TGPS) (n=25) and whole exome sequencing (WES) (n=20).

Results TGPS revealed causative mutations in four genes (IL10RA, EPCAM, TTC37 and SKIV2L) discovered unexpected phenotypes and directly influenced clinical decision making by supporting as well as avoiding haematopoietic stem cell transplantation. TGPS resulted in significantly higher median coverage when compared with WES, fewer coverage deficiencies and improved variant detection across established VEOIBD genes.

Conclusions Excluding or confirming known VEOIBD genotypes should be considered early in the disease course in all cases of therapy-refractory VEOIBD, as it can have a direct impact on patient management. To combine both described NGS technologies would compensate for the limitations of WES for disease-specific application while offering the opportunity for novel gene discovery in the research setting.

  • Genetics
  • Gastroenterology
  • Genetic screening/counselling
  • Inflammatory bowel disease
  • Molecular genetics

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