2020 Fiscal Year Final Research Report
Gene analysis for novel causative mutations in an inherited arrhythmia and determination of the underlying mechanism of arrhythmia
| Project/Area Number |
18K08100
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野村 章洋 金沢大学, 附属病院, 特任准教授 (30707542)
藤野 陽 金沢大学, 保健学系, 准教授 (40361993)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 遺伝性不整脈 / 次世代シーケンサー / 機能解析 |
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| Outline of Final Research Achievements |
Inherited arrhythmia can cause sudden cardiac death. It is important to determine the underlying mechanism and prevent the sudden cardiac death. We performed candidate gene analysis or whole exome sequence for inherited arrhythmia including long QT syndrome (n=66) Brugada syndrome (n=32), inherited bradyarrhythmia (n=32), arrhythmogenic right ventricular cardiomyopathy (n=17), and lone atrial fibrillation (n=6) using a next generation sequencer. We performed whole exome sequence of 23 probands diagnosed with early-onset (<65 years) inherited bradyarrhythmia and analysed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. Of 23 inherited bradyarrhythmia probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%).
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| Free Research Field |
不整脈
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| Academic Significance and Societal Importance of the Research Achievements |
次世代シーケンサ－による網羅的遺伝子解析により、従来の方法で見逃されていた数多くの遺伝子変異を見出すことができた。これまで機能解析が困難だった非イオンチャネル遺伝子に対し、CRISPR/Cas9システムを用いてゼブラフィッシュの遺伝子改変を行い、ゼブラフィッシュ胚の心臓の光学マッピング、活動電位測定、体表面心電図測定といった画期的な方法で数日間以内に遺伝子変異の病的意義を明らかにすることができた。
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