Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea. Issue 12 (December 2017)

• Record Type: Journal Article
• Authors: Petersen, Britt-Sabina; August, Dietrich; Abt, Renate; Alddafari, Moudjahed; Atarod, Lida; Baris, Safa; Bhavsar, Hemant; Brinkert, Florian; Buchta, Mary; Bulashevska, Alla; Chee, Ronnie; Cordeiro, Ana I.; Dara, Naghi; Dückers, Gregor; Elmarsafy, Aisha; Frede, Natalie; Galal, Nermeen; Gerner, Patrick; Glocker, Erik-Oliver; Goldacker, Sigune; Hammermann, Jutta; Hasselblatt, Peter; Havlicekova, Zuzana; Hübscher, Katrin; Jesenak, Milos; Karaca, Neslihan E.; Karakoc-Aydiner, Elif; Kharaghani, Mahboubeh M.; Kilic, Sara S.; Kiykim, Ayca; Klein, Christoph; Klemann, Christian; Kobbe, Robin; Kotlarz, Daniel; Laass, Martin W.; Leahy, T. Ronan; Mesdaghi, Mehrnaz; Mitton, Sally; Neves, João F.; Öztürk, Birol; Pereira, Luis F.; Rohr, Jan; Restrepo, Jessica L. R.; Ruzaike, Gunda; Saleh, Nadia; Seneviratne, Suranjith; Senol, Ebru; Speckmann, Carsten; Tegtmeyer, Daniel; Thankam, Paul; van der Werff ten Bosch, Jutte; von Bernuth, Horst; Zeissig, Sebastian; Zeissig, Yvonne; Franke, Andre; Grimbacher, Bodo;
• Is Part Of: Inflammatory bowel diseases. Volume 23:Issue 12(2017)
• Publication Date: 2017-12
• Subjects: early-onset IBD -- infant colitis -- chronic diarrhea -- next-generation sequencing -- genetic screening -- immunodeficiency; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000001235
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: 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. Abstract : Article first published online 19 September 2017.Supplemental Digital Content is Available in the Text.