Blood Advances (Jul 2017)
Whole-exome sequencing in evaluation of patients with venous thromboembolism
- Eun-Ju Lee,
- Daniel J. Dykas,
- Andrew D. Leavitt,
- Rodney M. Camire,
- Eduard Ebberink,
- Pablo García de Frutos,
- Kavitha Gnanasambandan,
- Sean X. Gu,
- James A. Huntington,
- Steven R. Lentz,
- Koen Mertens,
- Christopher R. Parish,
- Alireza R. Rezaie,
- Peter P. Sayeski,
- Caroline Cromwell,
- Noffar Bar,
- Stephanie Halene,
- Natalia Neparidze,
- Terri L. Parker,
- Adrienne J. Burns,
- Anne Dumont,
- Xiaopan Yao,
- Cassius Iyad Ochoa Chaar,
- Jean M. Connors,
- Allen E. Bale,
- Alfred Ian Lee
Affiliations
- Eun-Ju Lee
- Division of Hematology, Department of Internal Medicine, Weill Cornell Medical College, New York, NY;
- Daniel J. Dykas
- DNA Diagnostic Laboratory, Department of Genetics, Yale School of Medicine, New Haven, CT;
- Andrew D. Leavitt
- Department of Laboratory Medicine, San Francisco, CA; Department of Medicine, University of California, San Francisco, San Francisco, CA;
- Rodney M. Camire
- Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA;
- Eduard Ebberink
- Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands;
- Pablo García de Frutos
- Department of Cell Death and Proliferation, Institute of Biochemical Research, Barcelona, Spain;
- Kavitha Gnanasambandan
- Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL;
- Sean X. Gu
- Division of Hematology, Oncology, and Blood & Bone Marrow Transplantation, University of Iowa Carver College of Medicine, Iowa City, IA;
- James A. Huntington
- Department of Haematology, University of Cambridge, Cambridge, United Kingdom;
- Steven R. Lentz
- Division of Hematology, Oncology, and Blood & Bone Marrow Transplantation, University of Iowa Carver College of Medicine, Iowa City, IA;
- Koen Mertens
- Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands;
- Christopher R. Parish
- Department of Cancer Biology and Therapeutics, Australian National University, Canberra, Australia;
- Alireza R. Rezaie
- Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
- Peter P. Sayeski
- Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL;
- Caroline Cromwell
- Division of Hematology and Medical Oncology, Mount Sinai School of Medicine, New York, NY;
- Noffar Bar
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT;
- Stephanie Halene
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT;
- Natalia Neparidze
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT;
- Terri L. Parker
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT;
- Adrienne J. Burns
- Yale Cancer Center, New Haven, CT;
- Anne Dumont
- Yale Cancer Center, New Haven, CT;
- Xiaopan Yao
- Yale Center for Analytical Sciences, New Haven, CT;
- Cassius Iyad Ochoa Chaar
- Section of Vascular Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT
- Jean M. Connors
- Division of Hematology, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA
- Allen E. Bale
- DNA Diagnostic Laboratory, Department of Genetics, Yale School of Medicine, New Haven, CT;
- Alfred Ian Lee
- Section of Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT;; Alfred Ian Lee, Section of Hematology, Department of Internal Medicine, Yale School of Medicine, 333 Cedar St, Box 208028, New Haven, CT 06510;
- Journal volume & issue
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Vol. 1,
no. 16
pp. 1224 – 1237
Abstract
Abstract: Genetics play a significant role in venous thromboembolism (VTE), yet current clinical laboratory-based testing identifies a known heritable thrombophilia (factor V Leiden, prothrombin gene mutation G20210A, or a deficiency of protein C, protein S, or antithrombin) in only a minority of VTE patients. We hypothesized that a substantial number of VTE patients could have lesser-known thrombophilia mutations. To test this hypothesis, we performed whole-exome sequencing (WES) in 64 patients with VTE, focusing our analysis on a novel 55-gene extended thrombophilia panel that we compiled. Our extended thrombophilia panel identified a probable disease-causing genetic variant or variant of unknown significance in 39 of 64 study patients (60.9%), compared with 6 of 237 control patients without VTE (2.5%) (P 1 variant. Sanger sequencing performed in family members of 4 study patients with and without VTE showed generally concordant results with thrombotic history. WES and extended thrombophilia testing are promising tools for improving our understanding of VTE pathogenesis and identifying inherited thrombophilias.
