Details

Autor(en) / Beteiligte

• 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
• Amil Dias, Jorge
• Ben Hariz, Mongi
• Bourrier, Anne
• Breuer, Christian
• Breton, Anne
• Buderus, Stephan
• Cananzi, Mara
• Coopman, Stéphanie
• Crémilleux, Clara
• Dabadie, Alain
• Dumant-Forest, Clémentine
• Egritas Gurkan, Odul
• Fabre, Alexandre
• Fischer, Aude
• German Diaz, Marta
• 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
• Pinto Pais, Isabel
• Rebeuh, Julie
• Romano, Claudio
• Siala, Nadia
• Strisciuglio, Caterina
• Tempia-Caliera, Michela
• Tounian, Patrick
• Turner, Dan
• Urbonas, Vaidotas
• Willot, Stéphanie
• Ruemmele, Frank
• Cerf-Bensussan, Nadine N.

Titel

Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study

Ist Teil von

• Journal of Crohn's and colitis, 2018-09, Vol.12 (9), p.1104-1112

Ort / Verlag

Elsevier - Oxford University Press

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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 adapt treatment. Methods: 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.