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Comprehensive genetic and morphological analysis for sudden cardiac death autopsy cases

Research Project

Project/Area Number 21H03211
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 58040:Forensics medicine-related
Research InstitutionUniversity of Toyama

Principal Investigator

Hata Yukiko  富山大学, 学術研究部医学系, 准教授 (30311674)

Co-Investigator(Kenkyū-buntansha) 西田 尚樹  富山大学, 学術研究部医学系, 教授 (10315088)
一萬田 正二郎  富山大学, 学術研究部医学系, 助教 (60849355)
廣野 恵一  富山大学, 学術研究部医学系, 講師 (80456384)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2021: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords突然死 / エクソーム解析 / 病理組織学的検索 / 遺伝子変異 / 次世代シーケンサー / Molecular Autopsy / Sudden death / Exome analysis / 法医学 / exome analysis
Outline of Research at the Start

申請者の研究室で過去約10年間に次世代シーケンサー (NGS) によるパネルシーケンスを行ったものの病原遺伝子が特定されなかった心臓突然死35例と今後3年間で剖検されることが予想される心臓突然死約20例に対し,全エキソーム解析,挿入・欠失,コピー数変異の検索を行い,可能な症例は病原候補変異体の機能解析,家族解析を行って従来のサンガーシーケンスやパネルシーケンス法と比した病原遺伝子の検出率を検証する.
続いて,病原変異体が証明された症例に対し,刺激伝導系を含めた心臓の病理組織標本を画像解析にて網羅的に検索し,正常対照群と比較しながら軽微な病理学的変化が存在している可能性を検証する.

Outline of Final Research Achievements

The combined use of histopathological search and genetic analysis using next-generation sequencing was shown to be effective in determining the cause of death in autopsy cases of sudden cardiac death. In 65 autopsy cases of sudden cardiac death, including 35 undiagnosed cases, a variety of rare mutations were identified through whole exome analysis, and functional analysis and histopathological re-evaluation were performed. As a result, seven cases were diagnosed as known cardiomyopathies or channelopathies, and 15 cases were used to report the etiology and pathogenesis in a paper. This study demonstrated the importance of combining histopathological search and genetic analysis in elucidating the etiology and pathogenesis of sudden death and contributed to laying the foundation for improved diagnostic protocols.

Academic Significance and Societal Importance of the Research Achievements

心臓突然死の死因究明において、病理組織学的検索と次世代シークエンスを用いた遺伝子解析の併用が有効であることを示した。これにより、新たな病原性遺伝子変異の特定とその機能評価を通じて、心臓突然死の病因・病態の解明に寄与することができた。また、心臓突然死に関する診断基準の精度向上や、今後の研究の基盤を築く一助となった。診断精度の向上により、早期対応が可能となり、ご遺族への予防策の確立が期待される。さらに、社会全体の突然死予防に寄与することが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (14 results)

All 2024 2023 2022 2021 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (8 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Comprehensive pathological and genetic investigation of three young adult myotonic dystrophy type 1 patients with sudden unexpected death.2023

    • Author(s)
      Hata Y, Ichimata S, Yoshida K, Yamaguchi Y, Hirono K, Nishida N.
    • Journal Title

      J Neurol

      Volume: 270 Issue: 11 Pages: 5380-5391

    • DOI

      10.1007/s00415-023-11850-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathologic Appearance of Advanced Ketoacidosis With Basal Vacuolation in Renal Tubules2022

    • Author(s)
      Ichimata Shojiro、Hata Yukiko、Nishida Naoki
    • Journal Title

      Archives of Pathology & Laboratory Medicine

      Volume: 146 Issue: 9 Pages: 1102-1113

    • DOI

      10.5858/arpa.2021-0226-oa

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An autopsy case of sudden unexpected death with Barlow's disease2022

    • Author(s)
      Hata Yukiko、Tomita Naoko、Shibata Atsushi、Yokoyama Shigeki、Fukahara Kazuaki、Nishida Naoki
    • Journal Title

      Cardiovascular Pathology

      Volume: 61 Pages: 107462-107462

    • DOI

      10.1016/j.carpath.2022.107462

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An autopsy case of sudden unexpected death of a young adult with progressive intraventricular conduction delay2022

    • Author(s)
      Hata Yukiko、Hachiwaka Ryotaro、Ichimata Shojiro、Yamaguchi Yoshiaki、Nishida Naoki
    • Journal Title

      Pathology - Research and Practice

      Volume: 240 Pages: 154226-154226

    • DOI

      10.1016/j.prp.2022.154226

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction2021

    • Author(s)
      Hirono Keiichi、Hata Yukiko、Ozawa Sayaka Watanabe、Toda Takako、Momoi Nobuo、Fukuda Yutaka、Inuzuka Ryo、Nagamine Hiroki、Sakaguchi Heima、Kurosaki Kenichi、Okabe Mako、Takarada Shinya、Miyao Nariaki、Nakaoka Hideyuki、Ibuki Keijiro、Origasa Hideki、Bowles Neil E.、Nishida Naoki、Ichida Fukiko
    • Journal Title

      International Journal of Cardiology

      Volume: 328 Pages: 122-129

    • DOI

      10.1016/j.ijcard.2020.12.013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Pathological and comprehensive genetic investigation of autopsy cases of idiopathic bradyarrhythmia.2024

    • Author(s)
      Hata Y, Ichimata S, Hirono K, Yamaguchi Y, Oku Y, Ichida F, Nishida N.
    • Organizer
      第88回日本循環器学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 筋強直性筋ジストロフィーI型突然死剖検例の病理および遺伝子学的背景.2023

    • Author(s)
      畑由紀子,一萬田正二郎,西田尚樹.
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 進行性心室内伝導遅延を呈した若年者突然死の1剖検例.2023

    • Author(s)
      畑由紀子,一萬田正二郎,西田尚樹.
    • Organizer
      第107次日本法医学会学術全国集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Barlow症候群による心臓突然死の一剖検例2022

    • Author(s)
      畑由紀子,一萬田正二郎,西田尚樹
    • Organizer
      第44回 第69回 日本法医学会学術中部近畿地方集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Pathological and comprehensive genetic investigation of autopsy cases of idiopathic bradyarrhythmia2022

    • Author(s)
      畑由紀子, 一萬田正二郎, 廣野恵一, 山口由明, 市田蕗子, 西田尚樹
    • Organizer
      第68回日本不整脈心電学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] てんかんの病理と遺伝子検索2022

    • Author(s)
      西田尚樹, 畑由紀子
    • Organizer
      第5回法医分子病理研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Pathological and Comprehensive Genetic Investigation for Autopsy Cases with Advanced Bradyarrhythmia.2021

    • Author(s)
      畑由紀子,一萬田正二郎,西田尚樹.
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Emery-Dreifuss型筋ジストロフィーⅤによる心臓突然死と考えられた一剖検例.2021

    • Author(s)
      八若遼太朗,畑由紀子,一萬田正二郎,西田尚樹.
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Annual Research Report
  • [Remarks] 富山大学大学院医学薬学研究部(医学系)法医学講座_研究業績

    • URL

      http://www.med.u-toyama.ac.jp/legal/publications.html

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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