A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

Author:

Simeoni Ilenia12,Stephens Jonathan C.123,Hu Fengyuan14,Deevi Sri V. V.12,Megy Karyn12,Bariana Tadbir K.56,Lentaigne Claire78,Schulman Sol9,Sivapalaratnam Suthesh1310,Vries Minka J. A.11,Westbury Sarah K.12,Greene Daniel1213,Papadia Sofia12,Alessi Marie-Christine14,Attwood Antony P.123,Ballmaier Matthias15,Baynam Gareth1617181920,Bermejo Emilse21,Bertoli Marta22,Bray Paul F.23,Bury Loredana24,Cattaneo Marco25,Collins Peter26,Daugherty Louise C.12,Favier Rémi27,French Deborah L.28,Furie Bruce9,Gattens Michael29,Germeshausen Manuela15,Ghevaert Cedric13,Goodeve Anne C.30,Guerrero Jose A.1,Hampshire Daniel J.30,Hart Daniel P.10,Heemskerk Johan W. M.31,Henskens Yvonne M. C.11,Hill Marian32,Hogg Nancy33,Jolley Jennifer D.34,Kahr Walter H.35,Kelly Anne M.36,Kerr Ron37,Kostadima Myrto12,Kunishima Shinji38,Lambert Michele P.2839,Liesner Ri37,López José A.40,Mapeta Rutendo P.12,Mathias Mary37,Millar Carolyn M.78,Nathwani Amit6,Neerman-Arbez Marguerite41,Nurden Alan T.42,Nurden Paquita42,Othman Maha43,Peerlinck Kathelijne44,Perry David J.29,Poudel Pawan45,Reitsma Pieter46,Rondina Matthew T.47,Smethurst Peter A.135,Stevenson William4849,Szkotak Artur50,Tuna Salih12,van Geet Christel45,Whitehorn Deborah12,Wilcox David A.51,Zhang Bin52,Revel-Vilk Shoshana53,Gresele Paolo24,Bellissimo Daniel B.54,Penkett Christopher J.12,Laffan Michael A.78,Mumford Andrew D.1255,Rendon Augusto156,Gomez Keith56,Freson Kathleen45,Ouwehand Willem H.12357,Turro Ernest12313

Affiliation:

1. Department of Haematology, University of Cambridge,

2. National Institute for Health Research BioResource–Rare Diseases, Cambridge University Hospitals, and

3. National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom;

4. Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom;

5. The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London National Health Service Foundation Trust, London, United Kingdom;

6. Department of Haematology, University College London Cancer Institute, London, United Kingdom;

7. Centre for Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, and

8. Imperial College Healthcare National Health Service Trust, London, United Kingdom;

9. Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;

10. Department of Haematology, Barts Health National Health Service Trust, London, United Kingdom;

11. Department of Biochemistry, Maastricht University, Maastricht, The Netherlands;

12. School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom;

13. Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, United Kingdom;

14. Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Marseille, France;

15. Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;

16. School of Paediatrics and Child Health, The University of Western Australia, Crawley, Australia;

17. Western Australia Register of Developmental Anomalies, King Edward Memorial Hospital, Subiaco, Australia;

18. Office of Population Health Genomics, WA Department of Health, East Perth, Australia;

19. Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia;

20. Telethon Kids Institute, Subiaco, Australia;

21. Hematological Research Institute, National Academy of Medicine, Buenos Aires, Argentina;

22. San Pietro Fatebenefratelli Hospital, Unita' Operativa Semplice Dipartimentale, Medical Genetics, Rome, Italy;

23. Department of Medicine, Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA;

24. Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy;

25. Dipartimento di Scienze Della Salute, Università Degli Studi di Milano, Unità di Medicina, Azienda Ospedaliera San Paolo, Milan, Italy;

26. Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom;

27. Assistance Publique, Hôpitaux de Paris, Armand Trousseau Children Hospital, Paris, Inserm U1170, Villejuif, France;

28. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA;

29. Department of Haematology, Addenbrooke’s Hospital, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom;

30. Haemostasis Research Group, Department of Infection, Immunity and Cardiovascular Disease, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom;

31. Department of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands;

32. Department of Clinical Pathology, Empath Pathology Services, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom;

33. Cancer Research UK London Research Institute, London, United Kingdom;

34. Components Development Laboratory, National Health Service Blood and Transplant, Cambridge, United Kingdom;

35. Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada;

36. Department of Haematology, Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom;

37. Department of Haematology, Ninewells Hospital, Dundee, United Kingdom;

38. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan;

39. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;

40. Puget Sound Blood Center, Research Institute, Seattle, WA;

41. Department of Genetic Medicine and Development, University Medical Centre, Geneva, Switzerland;

42. Institut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France;

43. Department of Biomedical and Molecular Sciences, School of Medicine, Queens University, Kingston, Ontario, Canada;

44. Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium;

45. Institute of Cancer Research, London, United Kingdom;

46. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands;

47. University of Utah School of Medicine, Eccles Institute of Human Genetics, Salt Lake City, UT;

48. Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St. Leonards, NSW, Australia;

49. Kolling Institute of Medical Research, The University of Sydney, Sydney, Australia;

50. Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada;

51. Children’s Hospital of Wisconsin Research Institute, Medical College of Wisconsin, Milwaukee, WI;

52. Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, OH;

53. Pediatric Hematology/Oncology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;

54. Clinical Genomics Laboratory, University of Pittsburgh, Pittsburgh, PA;

55. School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;

56. Genomics England Limited, London, United Kingdom; and

57. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom

Abstract

Key Points Developed a targeted sequencing platform covering 63 genes linked to heritable bleeding, thrombotic, and platelet disorders. The ThromboGenomics platform provides a sensitive genetic test to obtain molecular diagnoses in patients with a suspected etiology.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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