Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Britt Sabina Petersen - , Kiel University (Author)
  • Dietrich August - , University Hospital of the Ruhr University Bochum (Author)
  • Renate Abt - , Nuremberg Clinic (Author)
  • Moudjahed Alddafari - , Abou Bakr Belkaïd University of Tlemcen (Author)
  • Lida Atarod - , Tehran University of Medical Sciences (Author)
  • Safa Baris - , Marmara University (Author)
  • Hemant Bhavsar - , Birmingham Women's and Children's NHS Foundation Trust (Author)
  • Florian Brinkert - , University of Hamburg (Author)
  • Mary Buchta - , University Hospital of the Ruhr University Bochum (Author)
  • Alla Bulashevska - , University Hospital of the Ruhr University Bochum (Author)
  • Ronnie Chee - , Royal Free London NHS Foundation Trust (Author)
  • Ana I. Cordeiro - , Hospital de Dona Estefânia (Author)
  • Naghi Dara - , Shahid Beheshti University of Medical Sciences (Author)
  • Gregor Dückers - , Helios Klinikum Krefeld (Author)
  • Aisha Elmarsafy - , Cairo University (Author)
  • Natalie Frede - , University Hospital of the Ruhr University Bochum (Author)
  • Nermeen Galal - , Cairo University (Author)
  • Patrick Gerner - , University of Freiburg (Author)
  • Erik Oliver Glocker - , University of Freiburg, Brandenburg Medical School Theodor Fontane (Author)
  • Sigune Goldacker - , University Hospital of the Ruhr University Bochum (Author)
  • Jutta Hammermann - , Department of Paediatrics, University Hospital Carl Gustav Carus Dresden (Author)
  • Peter Hasselblatt - , University Medical Center Freiburg (Author)
  • Zuzana Havlicekova - , Comenius University (Author)
  • Katrin Hübscher - , University Hospital of the Ruhr University Bochum (Author)
  • Milos Jesenak - , Comenius University (Author)
  • Neslihan E. Karaca - , Ege University (Author)
  • Elif Karakoc-Aydiner - , Marmara University (Author)
  • Mahboubeh M. Kharaghani - , Shahid Beheshti University of Medical Sciences (Author)
  • Sara S. Kilic - , Uludag University (Author)
  • Ayca Kiykim - , Marmara University (Author)
  • Christoph Klein - , Ludwig Maximilian University of Munich (Author)
  • Christian Klemann - , University Medical Center Freiburg, University of Freiburg (Author)
  • Robin Kobbe - , University of Hamburg (Author)
  • Daniel Kotlarz - , Ludwig Maximilian University of Munich (Author)
  • Martin W. Laass - , Department of Paediatrics, University Hospital Carl Gustav Carus Dresden (Author)
  • T. Ronan Leahy - , Our Lady's Hospital for Sick Children (Author)
  • Mehrnaz Mesdaghi - , Shahid Beheshti University of Medical Sciences (Author)
  • Sally Mitton - , University of London (Author)
  • João F. Neves - , Hospital de Dona Estefânia (Author)
  • Birol Öztürk - , Marmara University (Author)
  • Luis F. Pereira - , Hospital San Pedro de Alcántara (Author)
  • Jan Rohr - , University Hospital of the Ruhr University Bochum (Author)
  • Jessica L.R. Restrepo - , University Hospital of the Ruhr University Bochum (Author)
  • Gunda Ruzaike - , University of Freiburg (Author)
  • Nadia Saleh - , University of Bonn (Author)
  • Suranjith Seneviratne - , University College London (Author)
  • Ebru Senol - , Marmara University (Author)
  • Carsten Speckmann - , University Hospital of the Ruhr University Bochum (Author)
  • Daniel Tegtmeyer - , University of Freiburg (Author)
  • Paul Thankam - , University of London (Author)
  • Jutte Van Der Werff Ten Bosch - , Vrije Universiteit Brussel (Author)
  • Horst Von Bernuth - , Charité – Universitätsmedizin Berlin (Author)
  • Sebastian Zeissig - , Center for Regenerative Therapies Dresden, Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Yvonne Zeissig - , Department of Paediatrics, University Hospital Carl Gustav Carus Dresden (Author)
  • Andre Franke - , Kiel University (Author)
  • Bodo Grimbacher - , University Medical Center Freiburg (Author)

Abstract

Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.

Details

Original languageEnglish
Pages (from-to)2109-2120
Number of pages12
JournalInflammatory bowel diseases
Volume23
Issue number12
Publication statusPublished - 2017
Peer-reviewedYes

External IDs

PubMed 28930861

Keywords

Keywords

  • chronic diarrhea, early-onset IBD, genetic screening, immunodeficiency, infant colitis, next-generation sequencing