Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study. (18th May 2018)

• Record Type: Journal Article
• Authors: Charbit-Henrion, Fabienne; Parlato, Marianna; Hanein, Sylvain; Duclaux-Loras, Rémi; Nowak, Jan; Begue, Bernadette; Rakotobe, Sabine; Bruneau, Julie; Fourrage, Cécile; Alibeu, Olivier; Rieux-Laucat, Frédéric; Lévy, Eva; Stolzenberg, Marie-Claude; Mazerolles, Fabienne; Latour, Sylvain; Lenoir, Christelle; Fischer, Alain; Picard, Capucine; Aloi, Marina; Dias, Jorge Amil; Hariz, Mongi Ben; Bourrier, Anne; Breuer, Christian; Breton, Anne; Bronsky, Jiri; Buderus, Stephan; Cananzi, Mara; Coopman, Stéphanie; Crémilleux, Clara; Dabadie, Alain; Dumant-Forest, Clémentine; Gurkan, Odul Egritas; Fabre, Alexandre; Fischer, Aude; Diaz, Marta German; Gonzalez-Lama, Yago; Goulet, Olivier; Guariso, Graziella; Gurcan, Neslihan; Homan, Matjaz; Hugot, Jean-Pierre; Jeziorski, Eric; Karanika, Evi; Lachaux, Alain; Lewindon, Peter; Lima, Rosa; Magro, Fernando; Major, Janos; Malamut, Georgia; Mas, Emmanuel; Mattyus, Istvan; Mearin, Luisa M; Melek, Jan; Navas-Lopez, Victor Manuel; Paerregaard, Anders; Pelatan, Cecile; Pigneur, Bénédicte; Pais, Isabel Pinto; Rebeuh, Julie; Romano, Claudio; Siala, Nadia; Strisciuglio, Caterina; Tempia-Caliera, Michela; Tounian, Patrick; Turner, Dan; Urbonas, Vaidotas; Willot, Stéphanie; Ruemmele, Frank M; Cerf-Bensussan, Nadine;
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 9(2018:Sep.)
• Page Start: 1104
• Page End: 1112
• Publication Date: 2018-05-18
• Subjects: Genetics and molecular epidemiology -- paediatrics -- VEO-IBD -- monogenic disorders -- TNGS; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjy068
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [ n = 185] or an anamnesis suggestive of a monogenic disorder [ n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results: Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.