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Multicenter Study
. 2018 Aug 29;12(9):1104-1112.
doi: 10.1093/ecco-jcc/jjy068.

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study

Fabienne Charbit-Henrion  1   2   3   4 , Marianna Parlato  1   2   4 , Sylvain Hanein  5 , Rémi Duclaux-Loras  1   2   4 , Jan Nowak  1   2   4   6 , Bernadette Begue  1   2   4 , Sabine Rakotobe  1   2   4 , Julie Bruneau  2   7 , Cécile Fourrage  2   8 , Olivier Alibeu  2   9 , Frédéric Rieux-Laucat  2   10 , Eva Lévy  2   10 , Marie-Claude Stolzenberg  2   10 , Fabienne Mazerolles  2   10 , Sylvain Latour  2   11 , Christelle Lenoir  2   11 , Alain Fischer  2   12   13 , Capucine Picard  2   11   14 , Marina Aloi  4   15 , Jorge Amil Dias  4   16 , Mongi Ben Hariz  4   17 , Anne Bourrier  18 , Christian Breuer  4   19 , Anne Breton  4   20 , Jiri Bronsky  4   21 , Stephan Buderus  4   22 , Mara Cananzi  4   23 , Stéphanie Coopman  4   24 , Clara Crémilleux  4   25 , Alain Dabadie  4   26 , Clémentine Dumant-Forest  4   27 , Odul Egritas Gurkan  4   28 , Alexandre Fabre  4   29 , Aude Fischer  4   30 , Marta German Diaz  4   31 , Yago Gonzalez-Lama  32 , Olivier Goulet  2   3   4 , Graziella Guariso  4   33 , Neslihan Gurcan  4   28 , Matjaz Homan  4   34 , Jean-Pierre Hugot  4   35 , Eric Jeziorski  4   36 , Evi Karanika  4   37 , Alain Lachaux  4   38 , Peter Lewindon  4   39 , Rosa Lima  4   16 , Fernando Magro  40 , Janos Major  4   41 , Georgia Malamut  1   2   42 , Emmanuel Mas  4   20 , Istvan Mattyus  4   43 , Luisa M Mearin  4   44 , Jan Melek  4   45 , Victor Manuel Navas-Lopez  4   46 , Anders Paerregaard  4   47 , Cecile Pelatan  4   48 , Bénédicte Pigneur  1   2   3   4 , Isabel Pinto Pais  4   49 , Julie Rebeuh  4   50 , Claudio Romano  4   51 , Nadia Siala  4   52 , Caterina Strisciuglio  4   53 , Michela Tempia-Caliera  4   54 , Patrick Tounian  4   55 , Dan Turner  4   56 , Vaidotas Urbonas  4   57 , Stéphanie Willot  4   58 , Frank M Ruemmele  1   2   3   4 , Nadine Cerf-Bensussan  1   2   4
Affiliations
Multicenter Study

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study

Fabienne Charbit-Henrion et al. J Crohns Colitis. .

Erratum in

  • Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study.
    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 MC, Mazerolles F, Latour S, Lenoir C, Fischer A, Picard C, Aloi M, Dias JA, Hariz MB, Bourrier A, Breuer C, Breton A, Bronsky J, Buderus S, Cananzi M, Coopman S, Crémilleux C, Dabadie A, Dumant-Forest C, Gurkan OE, Fabre A, Fischer A, Diaz MG, Gonzalez-Lama Y, Goulet O, Guariso G, Gurcan N, Homan M, Hugot JP, 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, Pais IP, Rebeuh J, Romano C, Siala N, Strisciuglio C, Tempia-Caliera M, Tounian P, Turner D, Urbonas V, Willot S, Ruemmele FM, Cerf-Bensussan N. Charbit-Henrion F, et al. J Crohns Colitis. 2021 Mar 5;15(3):517-518. doi: 10.1093/ecco-jcc/jjaa164. J Crohns Colitis. 2021. PMID: 32895718 Free PMC article. No abstract available.

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.

Keywords: Genetics and molecular epidemiology; TNGS; VEO-IBD; monogenic disorders; paediatrics.

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Figures

Figure 1.
Figure 1.
Cohort screening for gene identification. Number of diagnoses obtained by each method. Number of patients for each gene defect is reported in brackets. WES: whole exome sequencing; TNGS: targeted next-generation sequencing.
Figure 2.
Figure 2.
Proposed algorithm for molecular diagnosis in VEO-IBD. VEO-IBD: very early-onset inflammatory bowel disease; CBC: cell blood count; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; Ig: immunoglobulin; GI: gastro-intestinal; AI: autoimmune; Ab: antibodies; Treg: regulatory T cells; small bowel inflam: small bowel inflammation; TNGS: targeted next-generation sequencing; WES: whole exome sequencing; WGS: whole genome sequencing.
See this image and copyright information in PMC

References

    1. Kammermeier J, Drury S, James CT, et al. . Targeted gene panel sequencing in children with very early onset inflammatory bowel disease – evaluation and prospective analysis. J Med Genet 2014;51:748–55. - PubMed
    1. Picard C, Fischer A. Contribution of high-throughput DNA sequencing to the study of primary immunodeficiencies. Eur J Immunol 2014;44:2854–61. - PubMed
    1. Uhlig HH. Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease. Gut 2013;62:1795–805. - PubMed
    1. Glocker EO, Kotlarz D, Boztug K, et al. . Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med 2009;361:2033–45. - PMC - PubMed
    1. Glocker EO, Frede N, Perro M, et al. . Infant colitis – it’s in the genes. Lancet 2010;376:1272. - PubMed

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