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Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study
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 m...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113703/ https://www.ncbi.nlm.nih.gov/pubmed/29788237 http://dx.doi.org/10.1093/ecco-jcc/jjy068 |
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author | 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 |
author_facet | 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 |
author_sort | Charbit-Henrion, Fabienne |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6113703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61137032018-09-04 Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study 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 J Crohns Colitis Original Articles 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. Oxford University Press 2018-08 2018-05-18 /pmc/articles/PMC6113703/ /pubmed/29788237 http://dx.doi.org/10.1093/ecco-jcc/jjy068 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles 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 Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study |
title | Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study |
title_full | Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study |
title_fullStr | Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study |
title_full_unstemmed | Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study |
title_short | Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study |
title_sort | diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: a multicentre study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113703/ https://www.ncbi.nlm.nih.gov/pubmed/29788237 http://dx.doi.org/10.1093/ecco-jcc/jjy068 |
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