{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:17:38Z","timestamp":1775265458401,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T00:00:00Z","timestamp":1526601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"crossref","award":["2015\/16\/T\/NZ5\/00168"],"award-info":[{"award-number":["2015\/16\/T\/NZ5\/00168"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjy068","type":"journal-article","created":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T11:09:27Z","timestamp":1526468967000},"page":"1104-1112","source":"Crossref","is-referenced-by-count":81,"title":["Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study"],"prefix":"10.1093","volume":"12","author":[{"given":"Fabienne","family":"Charbit-Henrion","sequence":"first","affiliation":[{"name":"INSERM, UMR1163, Laboratory of Intestinal Immunity, and Imagine Institute, Paris, France"},{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Paediatric Gastroenterology, Hepatology and Nutrition Unit, H\u00f4pital Necker-Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"}]},{"given":"Marianna","family":"Parlato","sequence":"additional","affiliation":[{"name":"INSERM, UMR1163, Laboratory of Intestinal Immunity, and Imagine Institute, Paris, France"},{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"}]},{"given":"Sylvain","family":"Hanein","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1163 Translational Genetic, and Imagine Institute, Paris, France"}]},{"given":"R\u00e9mi","family":"Duclaux-Loras","sequence":"additional","affiliation":[{"name":"INSERM, UMR1163, Laboratory of Intestinal Immunity, and Imagine Institute, Paris, France"},{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0953-2188","authenticated-orcid":false,"given":"Jan","family":"Nowak","sequence":"additional","affiliation":[{"name":"INSERM, UMR1163, Laboratory of Intestinal Immunity, and Imagine Institute, Paris, France"},{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland"}]},{"given":"Bernadette","family":"Begue","sequence":"additional","affiliation":[{"name":"INSERM, UMR1163, Laboratory of Intestinal Immunity, and Imagine Institute, Paris, France"},{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"}]},{"given":"Sabine","family":"Rakotobe","sequence":"additional","affiliation":[{"name":"INSERM, UMR1163, Laboratory of Intestinal Immunity, and Imagine Institute, Paris, France"},{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"}]},{"given":"Julie","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Pathology Department, H\u00f4pital Necker-Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}]},{"given":"C\u00e9cile","family":"Fourrage","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Bioinformatics Platform, Imagine Institute Paris, France"}]},{"given":"Olivier","family":"Alibeu","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Genomic Platform, Imagine Institute, Paris, France"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Rieux-Laucat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Immunogenetics of Paediatric Autoimmunity, and Imagine Institute, Paris, France"}]},{"given":"Eva","family":"L\u00e9vy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Immunogenetics of Paediatric Autoimmunity, and Imagine Institute, Paris, France"}]},{"given":"Marie-Claude","family":"Stolzenberg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Immunogenetics of Paediatric Autoimmunity, and Imagine Institute, Paris, France"}]},{"given":"Fabienne","family":"Mazerolles","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Immunogenetics of Paediatric Autoimmunity, and Imagine Institute, Paris, France"}]},{"given":"Sylvain","family":"Latour","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Lymphocyte activation and EBV susceptibility, and Imagine Institute, Paris, France"}]},{"given":"Christelle","family":"Lenoir","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Lymphocyte activation and EBV susceptibility, and Imagine Institute, Paris, France"}]},{"given":"Alain","family":"Fischer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Coll\u00e8ge de France, M\u00e9decine exp\u00e9rimentale, Paris, France"},{"name":"INSERM UMR 1163 and Imagine Institute, Paris, France"}]},{"given":"Capucine","family":"Picard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"INSERM, UMR1163, Lymphocyte activation and EBV susceptibility, and Imagine 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[GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Hopital La Marsa, Tunisia"}]},{"given":"Anne","family":"Bourrier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, H\u00f4pital St Antoine, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}]},{"given":"Christian","family":"Breuer","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Universit\u00e4tsklinikum Hamburg, Hamburg, Germany"}]},{"given":"Anne","family":"Breton","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Gastroenterology, Hepatology, Nutrition, and Diabetes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"}]},{"given":"Jiri","family":"Bronsky","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"University Hospital Motol, Prague, Czech Republic"}]},{"given":"Stephan","family":"Buderus","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"St. Marien Hospital, Bonn, Germany"}]},{"given":"Mara","family":"Cananzi","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Unit of Paediatric Hepatology, Department of Woman and Child Health, University Hospital of Padova, Padova, Italy"}]},{"given":"St\u00e9phanie","family":"Coopman","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne De Flandre Children\u2019s Hospital, Lille University Faculty of Medicine, Lille, France"}]},{"given":"Clara","family":"Cr\u00e9milleux","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Centre Hospitalo-Universitaire de St-Etienne, St-Etienne, France"}]},{"given":"Alain","family":"Dabadie","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Service de m\u00e9decine de l\u2019enfant et de l\u2019adolescent, H\u00f4pital Sud \u2013 Centre Hospitalo-Universitaire de Rennes, Rennes, France"}]},{"given":"Cl\u00e9mentine","family":"Dumant-Forest","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France"}]},{"given":"Odul Egritas","family":"Gurkan","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Paediatric Gastroenterology, Hepatology and Nutrition, Gazi University, Ankara, Turkey"}]},{"given":"Alexandre","family":"Fabre","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Assistance publique H\u00f4pitaux de Marseille, H\u00f4pital de la Timone, Marseille, France"}]},{"given":"Aude","family":"Fischer","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Centre Hospitalo-Universitaire Sud R\u00e9union, St Pierre, France"}]},{"given":"Marta German","family":"Diaz","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Unit of Paediatric Nutrition, Hospital Universitario 12 de Octubre, Madrid, Spain"}]},{"given":"Yago","family":"Gonzalez-Lama","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Unit, Hospital Universitario Puerta de Hierro\u2013Majadahonda, Madrid, Spain"}]},{"given":"Olivier","family":"Goulet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Paediatric Gastroenterology, Hepatology and Nutrition Unit, H\u00f4pital Necker-Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"}]},{"given":"Graziella","family":"Guariso","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"University of Padua, Italy"}]},{"given":"Neslihan","family":"Gurcan","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Paediatric Gastroenterology, Hepatology and Nutrition, Gazi University, Ankara, Turkey"}]},{"given":"Matjaz","family":"Homan","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Gastroenterology, Hepatology and Nutrition, University Children\u2019s Hospital, Ljubljana, Slovenia"}]},{"given":"Jean-Pierre","family":"Hugot","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Departments of Paediatric Digestive and Respiratory Diseases, H\u00f4pital Robert-Debr\u00e9, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}]},{"given":"Eric","family":"Jeziorski","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Infectious diseases and Immunology, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France"}]},{"given":"Evi","family":"Karanika","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, University General Hospital of 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Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Centre Hospitalo-Universitaire de Strasbourg, Strasbourg, France"}]},{"given":"Claudio","family":"Romano","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, Hospital of Messina, University of Messina, Messina, Italy"}]},{"given":"Nadia","family":"Siala","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, H\u00f4pital Mongi Slim, La Marsa, Tunisia"}]},{"given":"Caterina","family":"Strisciuglio","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Woman, Child and General and Specialized Surgery, Second University of Naples, Naples, Italy"}]},{"given":"Michela","family":"Tempia-Caliera","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatrics, FMH P\u00e9diatrie et FA Gastroent\u00e9rologie et h\u00e9patologie, Clinique des Grangettes, Geneva, Switzerland"}]},{"given":"Patrick","family":"Tounian","sequence":"additional","affiliation":[{"name":"GENIUS Group [GENetically ImmUne\u2013mediated enteropathieS] from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]"},{"name":"Department of Paediatric Nutrition and Gastroenterology, H\u00f4pital Armand Trousseau, Assistance Publique-H\u00f4pitaux de Paris, Paris, 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