PT - JOURNAL ARTICLE AU - Jochen Kammermeier AU - Suzanne Drury AU - Chela T James AU - Robert Dziubak AU - Louise Ocaka AU - Mamoun Elawad AU - Philip Beales AU - Nicholas Lench AU - Holm H Uhlig AU - Chiara Bacchelli AU - Neil Shah TI - Targeted gene panel sequencing in children with very early onset inflammatory bowel disease—evaluation and prospective analysis AID - 10.1136/jmedgenet-2014-102624 DP - 2014 Nov 01 TA - Journal of Medical Genetics PG - 748--755 VI - 51 IP - 11 4099 - http://jmg.bmj.com/content/51/11/748.short 4100 - http://jmg.bmj.com/content/51/11/748.full SO - J Med Genet2014 Nov 01; 51 AB - 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.