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The role of ECG and genetic variants in epilepsy

Research Project

Project/Area Number 18K08900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionJuntendo University

Principal Investigator

AI TOMOHIKO  順天堂大学, 医学部, 教授 (00570128)

Co-Investigator(Kenkyū-buntansha) 森 周介  東京医科歯科大学, 医学部附属病院, 助教 (20362072)
赤松 和土  順天堂大学, 大学院医学研究科, 教授 (60338184)
田部 陽子  順天堂大学, 大学院医学研究科, 教授 (70306968)
三井田 孝  順天堂大学, 大学院医学研究科, 教授 (80260545)
Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywordsてんかん / 心電図 / 予後予測 / 遺伝子検査 / DEPDC5 / 突然死 / 遺伝子 / 脳疾患 / けいれん / 性差 / 症候性 / 遺伝子解析 / iPS細胞 / 神経細胞 / 遺伝子異常 / 機能解析
Outline of Final Research Achievements

Epilepsy can cause trauma and sudden death. It also hurts other people if attacks occur during driving. However, it is difficult to predict when seizure attacks happen. Since brains and hearts physiologically regulate each other, we sought to investigate an association between ECG and timing of seizure attacks. Due to the COVID-19 pandemic, we could not perform prospective studies. Retrospective studies revealed that the patients who have structural brain diseases such as strokes and tumors showed abnormal cardiac repolarization (e.g., QT-prolongation). We also found that none of the patients did not have arrhythmias at epileptic attacks. In a different project, we firstly found that reduction of DEPDC5 gene in human iPS cells caused abnormal Ca2+-bursts.

Academic Significance and Societal Importance of the Research Achievements

てんかん発作が何時起こるかを予測する事は、脳波計測だけでは困難であった。また、てんかん関連突然死の原因は不明である。本研究成果では、心電図を用い、再分極過程(心臓興奮の回復過程)の異常を観察することで、てんかんの予後予測を行える可能性が示唆された。また、約90名のてんかん患者で発作直後に不整脈を起こしていた患者が認められなかった事より、てんかん関連突然死は、不整脈ではない可能性が示唆された。これらの結果は、心電図が、てんかん治療に有用である可能性が考えられる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2024 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Indiana University/Ohio State University/Invitae Laboratory(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Increased CaV1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly.2022

    • Author(s)
      Ozawa J, Ohno S, Melgari D, Wang Q, Fukuyama M, Toyoda F, Makiyama T, Yoshinaga M, Suzuki H, Saitoh A, Ai T, Horie M.
    • Journal Title

      Sci Rep

      Volume: 12 Issue: 1 Pages: 18984-18984

    • DOI

      10.1038/s41598-022-23512-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Abnormal Cardiac Repolarization After Seizure Episodes in Structural Brain Diseases: Cardiac Manifestation of Electrical Remodeling in the Brain?2021

    • Author(s)
      Mori S, Hori A, Turker I, Inaji M, Bello-Pardo E, Miida T, Otomo Y, Ai T
    • Journal Title

      J Am Heart Assoc

      Volume: 10 Issue: 9

    • DOI

      10.1161/jaha.120.019778

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel Variants in the CLCN1, RYR2, and DCTN1 Found in Elderly Japanese Dementia Patients: A Case Series2021

    • Author(s)
      Atsushi Hori, Tomohiko Ai, Miwa Isshiki, Yumiko Motoi, Kouji Yano, Yoko Tabe, Nobutaka Hattori, Takashi Miida
    • Journal Title

      Geriatrics

      Volume: 6 Issue: 1 Pages: 14-14

    • DOI

      10.3390/geriatrics6010014

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Telethonin variants found in Brugada syndrome, J-wave pattern ECG, and ARVC reduce peak Nav 1.5 currents in HEK-293 cells2020

    • Author(s)
      Turker I, Makiyama T, Ueyama T, Shimizu A, Yamakawa M, Chen PS, Vatta M, Horie M, Ai T
    • Journal Title

      Pacing Clin Electrophysiol

      Volume: 43 Issue: 8 Pages: 838-846

    • DOI

      10.1111/pace.13996

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study2020

    • Author(s)
      Morales A, Kinnamon DD, Jordan E, Platt J, Vatta M, Dorschner MO, Starkey CA, Mead JO, Ai T, Burke W, Gastier-Foster J, Jarvik GP, Rehm HL, Nickerson DA, Hershberger RE; DCM Precision Medicine study of the DCM Consortium
    • Journal Title

      Circ Genom Precis Med

      Volume: 13 Issue: 2

    • DOI

      10.1161/circgen.119.002480

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 薬剤抵抗性焦点性てんかん関連遺伝子であるDEPDC5のノックアウトは、ヒトiPS細胞由来神経細胞に異常なCa2+波を引き起こす2024

    • Author(s)
      Yuna Horiuchi, Haruka Inaba, Tetsuya Handoh, Tomohiko Ai, Takashi Miida
    • Organizer
      第101回日本生理学大会, 3/28-30, 北九州
    • Related Report
      2023 Annual Research Report
  • [Presentation] Ca2+-dysregulation caused by a CALM2 variant can be associated with neurodevelopmental disorders in patients with catecholaminergic polymorphic ventricular tachycardia2024

    • Author(s)
      Haruka Inaba, Tomohiko Ai, Takeru Makiyama, Jingshan Gao, Takashi Miida
    • Organizer
      Biophysical Meeting, Feb 2024, Philadelphia, PA, USA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] てんかん患者における脳腫瘍手術が心臓電気活動に与える影響2023

    • Author(s)
      森 周介、岩﨑 陽平、稲次 基希、藍 智彦
    • Organizer
      51回日本救急医学会総会・学術集会、東京
    • Related Report
      2023 Annual Research Report
  • [Presentation] 認知症患者で新たに発見されたCLCN1, RYR2及びDCTN1遺伝子変異: 認知症患者における遺伝子検査から得た教訓2020

    • Author(s)
      1.堀 敦詞, 藍 智彦, 本井 ゆみ子, 一色 美和, 田部 陽子, 平山 哲, 三井田 孝
    • Organizer
      第52回日本動脈硬化学会総会・学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] CRISPR Cas9 法による DEPDC5 欠損ヒト iPS 細胞の作製の試み2020

    • Author(s)
      堀 敦詞,藍 智彦,赤松 和土,三井田 孝
    • Organizer
      第60回日本臨床化学会年次学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 器質的脳疾患を有する患者と有さない患者間でのけいれん発作後の心電図の比較2020

    • Author(s)
      森 周介, 藍 智彦, 大友康裕
    • Organizer
      第47回日本集中治療医学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Variants In ARVC-Associated Genes Contribute To The Genetic Complexity Of Idiopathic DCM: An Initial Analysis From The DCM Precision Medicine Study2020

    • Author(s)
      Elizabeth Jordan, Daniel D. Kinnamon, Jonathan O. Mead, Garrie Haas, Tomohiko Ai, Laiken Peterson, Ray E. Hershberger
    • Organizer
      Heart Rhythm 2020 Scientific Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] けいれん発作後の心電図変化に関する検討2019

    • Author(s)
      森 周介
    • Organizer
      日本救急医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] アルツハイマー病関連遺伝子の次世代シークエンス解析を用いた網羅的検索2019

    • Author(s)
      堀 敦詞
    • Organizer
      日本臨床検査医学会
    • Related Report
      2019 Research-status Report
  • [Book] 不整脈2019 遺伝子病としての不整脈:遺伝子診断の光と影2019

    • Author(s)
      堀江稔、藍智彦
    • Total Pages
      238
    • Publisher
      メディカルレビュー
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] アルツハイマー病を標的とした治療2022

    • Inventor(s)
      Tomohiko Ai
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-000610
    • Filing Date
      2022
    • Related Report
      2022 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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