دورية أكاديمية
Whole-exome sequencing in evaluation of patients with venous thromboembolism
| العنوان: | Whole-exome sequencing in evaluation of patients with venous thromboembolism |
|---|---|
| المؤلفون: | Lee, Eun-Ju, Dykas, Daniel J., Leavitt, Andrew D., Camire, Rodney M., Ebberink, Eduard, García de Frutos, Pablo, Gnanasambandan, Kavitha, Gu, Sean X., Huntington, James Andrew, Lentz, Steven R., Mertens, Koen, Parish, Christopher R., Rezaie, Alireza R., Sayeski, Peter P., Cromwell, Caroline, Bar, Noffar, Halene, Stephanie, Neparidze, Natalia, Parker, Terri L., Burns, Adrienne J., Dumont, Anne, Yao, Xiaopan, Ochoa Chaar, Cassius Iyad, Connors, Jean M., Bale, Allen E., Lee, Alfred Ian |
| المساهمون: | National Health and Medical Research Council (Australia), National Institutes of Health (US), National Heart, Lung, and Blood Institute (US) |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2017 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | 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 < .0001). Clinical laboratory-based thrombophilia testing identified a heritable thrombophilia in only 14 of 54 study patients (25.9%). The majority of WES variants were either associated with thrombosis based on prior reports in the literature or predicted to affect protein structure based on protein modeling performed as part of this study. Variants were found in major thrombophilia genes, various SERPIN genes, and highly conserved areas of other genes with established or potential roles in coagulation or fibrinolysis. Ten patients (15.6%) had >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. ; C.R.P. was supported by the National Health and Medical Research Council of Australia. A.R.R. was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute R01 HL062565. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2473-9529 |
| العلاقة: | Publisher's version; https://doi.org/10.1182/bloodadvances.2017005249Test; Sí; Blood Advances 1(16): 1224-1237 (2017); http://hdl.handle.net/10261/176142Test; http://dx.doi.org/10.13039/501100000925Test; http://dx.doi.org/10.13039/100000002Test |
| DOI: | 10.1182/bloodadvances.2017005249 |
| DOI: | 10.13039/501100000925 |
| DOI: | 10.13039/100000002 |
| الإتاحة: | https://doi.org/10.1182/bloodadvances.2017005249Test https://doi.org/10.13039/501100000925Test https://doi.org/10.13039/100000002Test http://hdl.handle.net/10261/176142Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.4CF22A8 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 24739529 |
|---|---|
| DOI: | 10.1182/bloodadvances.2017005249 |