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

Fabienne Charbit-Henrion; Marianna Parlato; Sylvain Hanein; Rémi Duclaux-Loras; Jan Nowak; Bernadette Begue; Sabine Rakotobe; Julie Bruneau; Cécile Fourrage; Olivier Alibeu; Frédéric Rieux-Laucat; Eva Lévy; Marie-Claude Stolzenberg; Fabienne Mazerolles; Sylvain Latour; Christelle Lenoir; Alain Fischer; Capucine Picard; Marina Aloi; Jorge Amil Dias; Mongi Ben Hariz; Anne Bourrier; Christian Breuer; Anne Breton; Jiri Bronski; Stephan Buderus; Mara Cananzi; Stéphanie Coopman; Clara Crémilleux; Alain Dabadie; Clémentine Dumant-Forest; Odul Egritas Gurkan; Alexandre Fabre; Aude Fischer; Marta German Diaz; Yago Gonzalez-Lama; Olivier Goulet; Graziella Guariso; Neslihan Gurcan; Matjaz Homan; Jean-Pierre Hugot; Eric Jeziorski; Evi Karanika; Alain Lachaux; Peter Lewindon; Rosa Lima; Fernando Magro; Janos Major; Georgia Malamut; Emmanuel Mas; Istvan Mattyus; Luisa M Mearin; Jan Melek; Victor Manuel Navas-Lopez; Anders Paerregaard; Cecile Pelatan; Bénédicte Pigneur; Isabel Pinto Pais; Julie Rebeuh; Claudio Romano; Nadia Siala; Caterina Strisciuglio; Michela Tempia-Caliera; Patrick Tounian; Dan Turner; Vaidotas Urbonas; Stéphanie Willot; Frank M Ruemmele; Nadine Cerf-Bensussan

doi:10.1093/ecco-jcc/jjy068

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

Fabienne Charbit-Henrion, Marianna Parlato, Sylvain Hanein, Rémi Duclaux-Loras, Jan Nowak, Bernadette Begue, Sabine Rakotobe, Julie Bruneau, Cécile Fourrage, Olivier Alibeu, Frédéric Rieux-Laucat, Eva Lévy, Marie-Claude Stolzenberg, Fabienne Mazerolles, Sylvain Latour, Christelle Lenoir, Alain Fischer, Capucine Picard, Marina Aloi, Jorge Amil DiasMongi Ben Hariz, Anne Bourrier, Christian Breuer, Anne Breton, Jiri Bronski, Stephan Buderus, Mara Cananzi, Stéphanie Coopman, Clara Crémilleux, Alain Dabadie, Clémentine Dumant-Forest, Odul Egritas Gurkan, Alexandre Fabre, Aude Fischer, Marta German Diaz, Yago Gonzalez-Lama, Olivier Goulet, Graziella Guariso, Neslihan Gurcan, Matjaz Homan, Jean-Pierre Hugot, Eric Jeziorski, Evi Karanika, Alain Lachaux, Peter Lewindon, Rosa Lima, Fernando Magro, Janos Major, Georgia Malamut, Emmanuel Mas, Istvan Mattyus, Luisa M Mearin, Jan Melek, Victor Manuel Navas-Lopez, Anders Paerregaard, Cecile Pelatan, Bénédicte Pigneur, Isabel Pinto Pais, Julie Rebeuh, Claudio Romano, Nadia Siala, Caterina Strisciuglio, Michela Tempia-Caliera, Patrick Tounian, Dan Turner, Vaidotas Urbonas, Stéphanie Willot, Frank M Ruemmele, Nadine Cerf-Bensussan

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50 Citationer (Scopus)

Abstrakt

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.

Originalsprog	Engelsk
Tidsskrift	Journal of Crohn's & colitis
Vol/bind	12
Udgave nummer	9
Sider (fra-til)	1104-1112
ISSN	1873-9946
DOI	https://doi.org/10.1093/ecco-jcc/jjy068
Status	Udgivet - 29 aug. 2018

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10.1093/ecco-jcc/jjy068

Citationsformater

Charbit-Henrion, F., Parlato, M., Hanein, S., Duclaux-Loras, R., Nowak, J., Begue, B., Rakotobe, S., Bruneau, J., Fourrage, C., Alibeu, O., Rieux-Laucat, F., Lévy, E., Stolzenberg, M-C., Mazerolles, F., Latour, S., Lenoir, C., Fischer, A., Picard, C., Aloi, M., ... Cerf-Bensussan, N. (2018). Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study. Journal of Crohn's & colitis, 12(9), 1104-1112. https://doi.org/10.1093/ecco-jcc/jjy068

Charbit-Henrion, F, Parlato, M, Hanein, S, Duclaux-Loras, R, Nowak, J, Begue, B, Rakotobe, S, Bruneau, J, Fourrage, C, Alibeu, O, Rieux-Laucat, F, Lévy, E, Stolzenberg, M-C, Mazerolles, F, Latour, S, Lenoir, C, Fischer, A, Picard, C, Aloi, M, Amil Dias, J, Ben Hariz, M, Bourrier, A, Breuer, C, Breton, A, Bronski, J, Buderus, S, Cananzi, M, Coopman, S, Crémilleux, C, Dabadie, A, Dumant-Forest, C, Egritas Gurkan, O, Fabre, A, Fischer, A, German Diaz, M, Gonzalez-Lama, Y, Goulet, O, Guariso, G, Gurcan, N, Homan, M, Hugot, J-P, Jeziorski, E, Karanika, E, Lachaux, A, Lewindon, P, Lima, R, Magro, F, Major, J, Malamut, G, Mas, E, Mattyus, I, Mearin, LM, Melek, J, Navas-Lopez, VM, Paerregaard, A, Pelatan, C, Pigneur, B, Pinto Pais, I, Rebeuh, J, Romano, C, Siala, N, Strisciuglio, C, Tempia-Caliera, M, Tounian, P, Turner, D, Urbonas, V, Willot, S, Ruemmele, FM & Cerf-Bensussan, N 2018, 'Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study', Journal of Crohn's & colitis, bind 12, nr. 9, s. 1104-1112. https://doi.org/10.1093/ecco-jcc/jjy068

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

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 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.",

author = "Fabienne Charbit-Henrion and Marianna Parlato and Sylvain Hanein and R{\'e}mi Duclaux-Loras and Jan Nowak and Bernadette Begue and Sabine Rakotobe and Julie Bruneau and C{\'e}cile Fourrage and Olivier Alibeu and Fr{\'e}d{\'e}ric Rieux-Laucat and Eva L{\'e}vy and Marie-Claude Stolzenberg and Fabienne Mazerolles and Sylvain Latour and Christelle Lenoir and Alain Fischer and Capucine Picard and Marina Aloi and {Amil Dias}, Jorge and {Ben Hariz}, Mongi and Anne Bourrier and Christian Breuer and Anne Breton and Jiri Bronski and Stephan Buderus and Mara Cananzi and St{\'e}phanie Coopman and Clara Cr{\'e}milleux and Alain Dabadie and Cl{\'e}mentine Dumant-Forest and {Egritas Gurkan}, Odul and Alexandre Fabre and Aude Fischer and {German Diaz}, Marta and Yago Gonzalez-Lama and Olivier Goulet and Graziella Guariso and Neslihan Gurcan and Matjaz Homan and Jean-Pierre Hugot and Eric Jeziorski and Evi Karanika and Alain Lachaux and Peter Lewindon and Rosa Lima and Fernando Magro and Janos Major and Georgia Malamut and Emmanuel Mas and Istvan Mattyus and Mearin, {Luisa M} and Jan Melek and Navas-Lopez, {Victor Manuel} and Anders Paerregaard and Cecile Pelatan and B{\'e}n{\'e}dicte Pigneur and {Pinto Pais}, Isabel and Julie Rebeuh and Claudio Romano and Nadia Siala and Caterina Strisciuglio and Michela Tempia-Caliera and Patrick Tounian and Dan Turner and Vaidotas Urbonas and St{\'e}phanie Willot and Ruemmele, {Frank M} and Nadine Cerf-Bensussan",

year = "2018",

month = aug,

day = "29",

doi = "10.1093/ecco-jcc/jjy068",

language = "English",

volume = "12",

pages = "1104--1112",

journal = "Journal of Crohn's and Colitis",

issn = "1873-9946",

publisher = "Elsevier BV",

number = "9",

}

TY - JOUR

T1 - Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases

T2 - A Multicenter Study

AU - Charbit-Henrion, Fabienne

AU - Parlato, Marianna

AU - Hanein, Sylvain

AU - Duclaux-Loras, Rémi

AU - Nowak, Jan

AU - Begue, Bernadette

AU - Rakotobe, Sabine

AU - Bruneau, Julie

AU - Fourrage, Cécile

AU - Alibeu, Olivier

AU - Rieux-Laucat, Frédéric

AU - Lévy, Eva

AU - Stolzenberg, Marie-Claude

AU - Mazerolles, Fabienne

AU - Latour, Sylvain

AU - Lenoir, Christelle

AU - Fischer, Alain

AU - Picard, Capucine

AU - Aloi, Marina

AU - Amil Dias, Jorge

AU - Ben Hariz, Mongi

AU - Bourrier, Anne

AU - Breuer, Christian

AU - Breton, Anne

AU - Bronski, Jiri

AU - Buderus, Stephan

AU - Cananzi, Mara

AU - Coopman, Stéphanie

AU - Crémilleux, Clara

AU - Dabadie, Alain

AU - Dumant-Forest, Clémentine

AU - Egritas Gurkan, Odul

AU - Fabre, Alexandre

AU - Fischer, Aude

AU - German Diaz, Marta

AU - Gonzalez-Lama, Yago

AU - Goulet, Olivier

AU - Guariso, Graziella

AU - Gurcan, Neslihan

AU - Homan, Matjaz

AU - Hugot, Jean-Pierre

AU - Jeziorski, Eric

AU - Karanika, Evi

AU - Lachaux, Alain

AU - Lewindon, Peter

AU - Lima, Rosa

AU - Magro, Fernando

AU - Major, Janos

AU - Malamut, Georgia

AU - Mas, Emmanuel

AU - Mattyus, Istvan

AU - Mearin, Luisa M

AU - Melek, Jan

AU - Navas-Lopez, Victor Manuel

AU - Paerregaard, Anders

AU - Pelatan, Cecile

AU - Pigneur, Bénédicte

AU - Pinto Pais, Isabel

AU - Rebeuh, Julie

AU - Romano, Claudio

AU - Siala, Nadia

AU - Strisciuglio, Caterina

AU - Tempia-Caliera, Michela

AU - Tounian, Patrick

AU - Turner, Dan

AU - Urbonas, Vaidotas

AU - Willot, Stéphanie

AU - Ruemmele, Frank M

AU - Cerf-Bensussan, Nadine

PY - 2018/8/29

Y1 - 2018/8/29

N2 - 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.

AB - 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.

U2 - 10.1093/ecco-jcc/jjy068

DO - 10.1093/ecco-jcc/jjy068

M3 - Journal article

C2 - 29788237

VL - 12

SP - 1104

EP - 1112

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 9

ER -

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

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