• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of mechanism of cardiac calcium channel (CaV1.2) abnormality in long QT syndrome

Research Project

Project/Area Number 17K15999
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionShiga University of Medical Science

Principal Investigator

Fukuyama Megumi  滋賀医科大学, 医学部, 助教 (60625771)

Research Collaborator Ohno Seiko  
Horie Minoru  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsQT延長症候群8型 / CACNA1C遺伝子 / QT延長症候群 / CACNA1C遺伝子変異 / リアノジン受容体遺伝子 / 循環器 / 家族性不整脈症候群 / 遺伝子
Outline of Final Research Achievements

In a cohort of about 5000 of inherited lethal arrhythmic patients we collected, 892 LQTS patients who identified no mutation genes while exhibiting QT prolongation were extracted and searched for CACNA1C gene mutations. As a result, CACNA1C mutations were identified in 17 probands, including 3 probands with classical Timothy syndrome.
As a result of analyzing the clinical and electrocardiographic characteristics in these LQT8 patients, the cases with late-appearance T wave showed severe clinical phenotypes at a high rate. It was suggested that the larger of calcium current by mutation lead to the late-appearance T wave changes. We made a paper comparing this feature with LQT3, which exhibits similar ECG changes (currently being submitted to the peer review journal).

Academic Significance and Societal Importance of the Research Achievements

まず従来は非常に稀で重篤な臨床像を呈すると考えられてきたLQT8の同定率がLQT3に匹敵するほど高く、心電図異常以外の症状を呈さない軽症例も存在することが明らかとなり、実臨床にてLQT患者の診療にあたる上で重要な事実となった。またこれらLQT8患者の心電図学的特徴とイオンチャネルの機能変化・臨床像の重症度を紐づけることで、LQT8患者の中でもハイリスク群に属する患者を予測することができ、治療や安全管理の上で非常に役立つと考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (15 results) (of which Int'l Joint Research: 9 results)

  • [Journal Article] Novel intracellular transport-refractory mutations in KCNH2 identified in patients with symptomatic long QT syndrome2018

    • Author(s)
      Fukumoto Daisuke、Ding Wei-Guang、Wada Yuko、Fujii Yusuke、Ichikawa Mari、Takayama Koichiro、Fukuyama Megumi、Kato Koichi、Itoh Hideki、Makiyama Takeru、Omatsu-Kanbe Mariko、Matsuura Hiroshi、Horie Minoru、Ohno Seiko
    • Journal Title

      Journal of Cardiology

      Volume: 71 Issue: 4 Pages: 401-408

    • DOI

      10.1016/j.jjcc.2017.10.004

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Usefulness of Genetic Screening for Long QT syndrome in the School-Based Electrocardiographic Screening Programs2019

    • Author(s)
      福山 恵, 大野 聖子, 小澤 淳一, 髙山 幸一郎, 加藤 浩一, 伊藤 英樹, 青木 寿明, 牧山 武, 堀江 稔
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Excessive Ca2+ Release from Ryanodine Receptors Underlying a RyR2 Mutation Associated with Catecholaminergic Polymorphic Ventricular Tachycardia2019

    • Author(s)
      伊藤 英樹, 村山 尚, 呉林 なごみ, 大野 聖子, 藤居 祐介, 加藤 浩一, 福山 恵, 髙山 幸一郎, 渡邉 昌也, 安斉 俊久, 堀江 稔
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] An NGS-based genotyping in LQTS; minor genes are no longer minor2019

    • Author(s)
      Seiko Ohno, Junichi Ozawa, Megumi Fukuyama, Takeru Makiyama, Minoru Horie
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Ebstein病に左室緻密化障害を合併した心室頻拍の一例2019

    • Author(s)
      西川拓磨, 小澤友哉, 奥谷雄介, 藤居祐介, 加藤浩一, 福山 恵, 芦原貴司, 山本 孝
    • Organizer
      第126回日本循環器学会近畿地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Consideration of CACNA1C variants in Long QT Syndrome2018

    • Author(s)
      Megumi Fukuyama, Seiko Ohno, Minoru Horie
    • Organizer
      第65回日本不整脈心電学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] How to Confirm the Pathogenicity of Gene Variants in Inherited Primary Arrhythmia Syndrome.2018

    • Author(s)
      Fukuyama M, Ohno S, Takayama K, Ichikawa M, Fukumoto D, Horie M.
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel RYR2 mutations causative for long QT syndromes.2017

    • Author(s)
      Fukuyama M, Ohno S, Takayama K, Ichikawa M, Horie M.
    • Organizer
      ESC Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] SCN10A Mutations Related with Bradycardia and Conduction Block in Young Patients.2017

    • Author(s)
      Aoki H, Ohno S, Fukuyama M, Yoshinaga M, Horie M.
    • Organizer
      ESC Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Double mutations in RYR2 cause severe phenotype of catecholaminergic polymorphic ventricular tachycardia2017

    • Author(s)
      Takayama K, Ohno S, Fukumoto D, Wada Y, Ichikawa M, Fukuyama M, Itoh H, Horie M.
    • Organizer
      ESC Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel intracellular transport-refractory mutations in KCNH2 identified in symptomatic long QT syndrome patients2017

    • Author(s)
      Fukumoto D, Ohno S, Wada Y, Fujii Y, Ichikawa M, Takayama K, Fukuyama M, Makiyama T, Itoh H, Ding WG, Matsuura H, Horie M.
    • Organizer
      ESC Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of copy number variations by next generation sequencer in patients with inherited primary arrhythmia syndromes.2017

    • Author(s)
      Ichikawa M, Ohno S, Fukumoto D, Takayama K, Wada Y, Fukuyama M, Makiyama T, Itoh H, Horie M.
    • Organizer
      ESC Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] High frequency of CACNA1C mutations among genotyped LQTS patients2017

    • Author(s)
      Ohno S, Ozawa J, Fukuyama M, Horie M.
    • Organizer
      ESC Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel RYR2 Mutations Causative for Long QT Syndromes.2017

    • Author(s)
      Fukuyama M, Ohno S, Takayama K, Ichikawa M, Fukumoto D, Horie M.
    • Organizer
      APHRS2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Next-Generation Sequencing Is One of the Promising Ways for Identifying Copy Number Variations in Patients with Inherited Primary Arrhythmia Syndromes.2017

    • Author(s)
      Ichikawa M, Ohno S, Fukumoto D, Takayama K, Wada Y, Fukuyama M, Makiyama T, Itoh H, Horie M.
    • Organizer
      APHRS2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel N-Terminal KCNH2 Mutations Identified in Symptomatic Long QT Syndrome Patients.2017

    • Author(s)
      Fukumoto D, Ohno S, Wada Y, Fujii Y, Ichikawa M, Takayama K, Fukuyama M, Itoh H, Ding WG, Matsuura H, Horie M.
    • Organizer
      APHRS2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi