Petersen, BSAugust, DAbt, RAlddafari, MAtarod, LBaris, SBhavsar, HBrinkert, FBuchta, MBulashevska, AChee, RCordeiro, AIDara, NDückers, GElmarsafy, AFrede, NGalal, NGerner, PGlocker, EOGoldacker, SHammermann, JHasselblatt, PHavlicekova, ZHübscher, KJesenak, MKaraca, NEKarakoc-Aydiner, EKharaghani, MMKilic, SSKiykim, AKlein, CKlemann, CKobbe, RKotlarz, DLaass, MWLeahy, TRMesdaghi, MMitton, SFarela Neves, JÖztürk, BPereira, LFRohr, JRestrepo, JLRRuzaike, GSaleh, NSeneviratne, SSenol, ESpeckmann, CTegtmeyer, DThankam, Pvan der Werff ten Bosch, Jvon Bernuth, HZeissig, SZeissig, YFranke, AGrimbacher, B2023-11-032023-11-032017Inflamm Bowel Dis . 2017 Dec;23(12):2109-2120http://hdl.handle.net/10400.17/4726Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.engChild, PreschoolChildChronic DiseaseDiarrhea / etiology*Exome SequencingGenetic Predisposition to Disease*Genome-Wide Association StudyHigh-Throughput Nucleotide SequencingInfant, NewbornInflammatory Bowel Diseases / genetics*MutationHDE PEDjournal article10.1097/MIB.0000000000001235