Targeted next-generation sequencing reveals novel and known variants of thrombophilia associated genes in Saudi patients with venous thromboembolism
| Autor: | G. G. H. A. Shadab, Amani A. Albagenny, Mohammad M. Alkazmi, Neda M. Bogari, Mohammad M. Alkhuzae, Abdulaziz A. Althebyani, Khalid Alquthami, Saeed H. Halawani, Zainularifeen Abduljaleel, Mohammad Athar, Anas Dannoun, Ahmed Elsendiony, Ibrahim S. Ghita, Faisal A. Al-Allaf |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Candidate gene Clinical Biochemistry Saudi Arabia Bioinformatics Thrombophilia Biochemistry DNA sequencing 03 medical and health sciences 0302 clinical medicine Factor V Leiden Humans Medicine Gene Methylenetetrahydrofolate Reductase (NADPH2) biology business.industry Biochemistry (medical) Factor V High-Throughput Nucleotide Sequencing Venous Thromboembolism General Medicine Ion semiconductor sequencing medicine.disease Venous thrombosis 030104 developmental biology 030220 oncology & carcinogenesis Methylenetetrahydrofolate reductase biology.protein business |
| Zdroj: | Clinica Chimica Acta. 519:247-254 |
| ISSN: | 0009-8981 |
| Popis: | Background Thrombophilia is a substantial source of indisposition and mortality in several countries, including Arab populations. Deep venous thrombosis (DVT) with or without pulmonary embolism (PE) is the prevalent clinical manifestation of thrombophilia. While many genetic risk factors for DVT are known, almost all associated with hemostasis, many genetic factors remain unexplained. Nowadays, Next Generation Sequencing (NGS) offers a potential solution that allows several candidate genes to be analyzed simultaneously at a reasonable expense. Methods We performed variant screening in the thrombophilia associated genes in Factor V Leiden (FVL) mutation-negative patients using Ion Torrent Next-generation sequencing (NGS). Ion AmpliSeq panel for 18 genes was designed. Twenty-nine unrelated patients with idiopathic VTE were recruited for NGS. Results We were able to identify 19 variants (1 novel and 18 previously reported) in 10 out of 18 targeted genes. Pathogenic variants were identified in 22 patients demonstrating mutation detection rates of 76%. Previously reported variants in the F5, MTHFR, PROS1, PROC, F8, F9, SERPINA10, SERPIND1, and HRG genes were recognized in 21 patients. More than one variant in the targeted genes was detected in some of the patients with VTE. We identified SERPINA10 recurrent variant p.(R88*) in seven patients representing 32% of VTE cases. Additionally, we report one novel variant c.356G > T, p.(G119V) in the F7 gene, considered to be pathogenic in this study. Conclusions Our studies finding illustrates the ability of targeted next-generation sequencing to uncover uncommon/unknown genetic variants that may predispose to thrombophilia. The finding of the novel variant in the F7 gene extends the spectrum of variants affecting thrombosis. While a comparatively small number of subjects have been included in our cohort, the findings summarize the possible genetic features of thrombophilia. |
| Databáze: | OpenAIRE |
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