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Targeted Gene Panel Sequencing for Early-Onset Inflammatory Bowel Disease and Chronic Diarrhea Publisher Pubmed



Petersen BS1 ; August D2 ; Abt R3 ; Alddafari M4 ; Atarod L5 ; Baris S6 ; Bhavsar H7 ; Brinkert F8 ; Buchta M2 ; Bulashevska A2 ; Chee R9 ; Cordeiro AI10 ; Dara N11 ; Duckers G12 Show All Authors
Authors
  1. Petersen BS1
  2. August D2
  3. Abt R3
  4. Alddafari M4
  5. Atarod L5
  6. Baris S6
  7. Bhavsar H7
  8. Brinkert F8
  9. Buchta M2
  10. Bulashevska A2
  11. Chee R9
  12. Cordeiro AI10
  13. Dara N11
  14. Duckers G12
  15. Elmarsafy A13
  16. Frede N2
  17. Galal N13
  18. Gerner P14
  19. Glocker EO15, 38
  20. Goldacker S2
  21. Hammermann J16
  22. Hasselblatt P17
  23. Havlicekova Z18
  24. Hubscher K2
  25. Jesenak M18
  26. Karaca NE19
  27. Karakocaydiner E6
  28. Kharaghani MM20
  29. Kilic SS21
  30. Kiykim A6
  31. Klein C22
  32. Klemann C23, 24
  33. Kobbe R8
  34. Kotlarz D22
  35. Laass MW16
  36. Leahy TR25
  37. Mesdaghi M26
  38. Mitton S27
  39. Neves JF10
  40. Ozturk B28
  41. Pereira LF29
  42. Rohr J2
  43. Restrepo JLR2
  44. Ruzaike G30
  45. Saleh N31
  46. Seneviratne S32
  47. Senol E28
  48. Speckmann C2
  49. Tegtmeyer D14
  50. Thankam P33
  51. Van Der Werff Ten Bosch J34
  52. Von Bernuth H35
  53. Zeissig S36, 37
  54. Zeissig Y16
  55. Franke A1
  56. Grimbacher B2
Show Affiliations
Authors Affiliations
  1. 1. Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
  2. 2. Center for Chronic Immunodeficiency (CCI), DZIF Satellite Center, Medical Center, Faculty of Medicine, Germany
  3. 3. Paediatric Gastroenterology, Klinikum Nurnberg, Nuremberg, Germany
  4. 4. Laboratory of Applied Molecular Biology and Immunology, University of Abou-Bekr Belkaid, Tlemcen, Algeria
  5. 5. Department of Pediatrics, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Clinic of Pediatric Allergy and Immunology, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey
  7. 7. Department of Gastroenterology and Clinical Nutrition, Birmingham Children's Hospital, Birmingham, United Kingdom
  8. 8. Department of Paediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  9. 9. Department of Immunology, Royal Free Hospital, London, United Kingdom
  10. 10. Primary Immunodeficiencies Unit, Hospital Dona Estefania, Pediatric University Hospital, CEDOC, Chronic Diseases Research Center, NOVA Medical School, Lisbon, Portugal
  11. 11. Department of Pediatric Gasteroentrology and Hepatology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  12. 12. Helios Kliniken, Childrens Hospital, Krefeld, Germany
  13. 13. Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt
  14. 14. Paediatric Gastroenterology/Hepatology, University of Freiburg, Freiburg, Germany
  15. 15. Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany
  16. 16. Department of Pediatrics, University Medical Center Dresden, Technische Universitat Dresden, Dresden, Germany
  17. 17. Department of Medicine II, University Hospital, Medical Faculty, University Freiburg, Freiburg, Germany
  18. 18. Department of Paediatrics, Centre for Diagnosis and Treatment of Primary Immunodeficiencies, Jessenius Faculty of Medicine, Commenius University in Bratislava, Martin, Slovakia
  19. 19. Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey
  20. 20. Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  21. 21. Pediatric Immunology Division, Uludag University Medical Faculty, Department of Pediatrics, Bursa, Turkey
  22. 22. Dr. von Hauner Children's Hospital, Department of Pediatrics, Ludwig-Maximilians-Universitat Munich, Munich, Germany
  23. 23. Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
  24. 24. Center for Pediatrics, Department of Pediatric Hematology and Oncology, University Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
  25. 25. Department of Paediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital, Dublin, Ireland
  26. 26. Department of Immunology, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  27. 27. Department of Paediatric Gastroenterology, St. George's Healthcare NHS Trust, University of London, London, United Kingdom
  28. 28. Department of Gastroenterology and Clinical Nutrition, Marmara University Medical Faculty, Istanbul, Turkey
  29. 29. Service of Clinical Laboratory, Division of Immunology, San Pedro de Alcantara Hospital, Caceres, Spain
  30. 30. Bone Marrow Failure Group, Division of Pediatric Hematology and Oncology, University of Freiburg, Germany
  31. 31. Children's Hospital, University of Bonn, Germany
  32. 32. University College London, Institute of Immunity and Transplantation, Royal Free Campus, London, United Kingdom
  33. 33. Department of Paediatrics, St. George's Hospital, University of London, London, United Kingdom
  34. 34. Department of Pediatrics, Universitair Ziekenhuis Brussel, Brussels, Belgium
  35. 35. Pediatric Pneumology and Immunology, Department of Immunology, Charite University Medicine Labor Berlin Charite Vivantes GmbH, Berlin, Germany
  36. 36. Department of Medicine i, University Medical Center Dresden, Technische Universitat Dresden, Dresden, Germany
  37. 37. Center for Regenerative Therapies, Technische Universitat Dresden, Dresden, Germany
  38. 38. Institute of Laboratory Medicine, Brandenburg Hospital, Brandenburg Medical School, Brandenburg/Havel, Germany

Source: Inflammatory Bowel Diseases Published:2017


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. © 2017 Oxford University Press. All rights reserved.
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