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Clinical and genetic analysis and identifiction of casative genes for adult leukoencephalopathy

Research Project

Project/Area Number 18K15459
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionYokohama City University

Principal Investigator

Miyake Ryoko  横浜市立大学, 医学研究科, 客員研究員 (10760184)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsleukoencephalopathy / exome / NOTCH2NLC / 白質脳症 / エクソーム解析 / 原因遺伝子 / 遺伝子解析
Outline of Final Research Achievements

Leukoencephalopathies comprise a broad spectrum of disorders, but the genetic background of adult leukoencephalopathies has rarely been assessed. We analyzed 110 Japanese patients with adult leukoencephalopathy using custom-designed gene panel (CDGP), whole-exome sequencing (WES) and repeat-primed PCR (RP-PCR) for detecting GGC expansion in NOTCH2NLC, which was identified as the cause of neuronal intranuclear inclusion disease (NIID). As for CDGP and WES, the patients with “likely pathogenic” and “pathogenic” variants were picked up according to American College of Medical Genetics guidelines.
As the results of CDGP and WES, we found 11 patients with “likely pathogenic” / “pathogenic” NOTCH3 variants as the major cause of adult leukoencephalopathy detectable by short-read sequencing. As the result of RP-PCR, we found 12 patients with GGC expansion in NOTCH2NLC. Our results indicate that NIID and CADASIL are two major causes of Japanese adult non-acquired leukoencephalopathy.

Academic Significance and Societal Importance of the Research Achievements

成人白質脳症において多検体を用いて遺伝学的背景の解明を試みた研究は少なく、イギリス、ブラジルの施設で行われた研究(Lynch DSらBrain 140, 1204-1211, 2017)以外ほとんど見当たらない。我々は日本人成人白質脳症患者において110例(先行研究と合わせてた症例数)のうち28例(25.5%)において原因遺伝子を明らかにし、12例がNIID、11例がCADASILでNIIDとCADASILであることを示した。上記2疾患が日本人成人白質脳症の2大原因であることを明らかにした(Okubo Mら、業績参照)ことは、実臨床に非常に有益な情報を与えるものであると考えられる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy2019

    • Author(s)
      Okubo Masaki、Doi Hiroshi、et al.
    • Journal Title

      Annals of Neurology

      Volume: 86 Issue: 6 Pages: 962-968

    • DOI

      10.1002/ana.25586

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Non-traumatic Acute Epidural Hematoma in Multiple Sclerosis Treated With Fingolimod2019

    • Author(s)
      Fukai Ryoko、Takahashi Keita、Abe Hiroyuki、Higashiyama Yuichi、Doi Hiroshi、Takeuchi Hideyuki、Tanaka Fumiaki
    • Journal Title

      Frontiers in Neurology

      Volume: 10 Pages: 763-763

    • DOI

      10.3389/fneur.2019.00763

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An acute encephalopathy with reduced diffusion in BRAF-associated cardio-facio-cutaneous syndrome2019

    • Author(s)
      Okuzono Sayaka、Fukai Ryoko、Noda Marie、Miyake Noriko、Lee Sooyoung、Kaku Noriyuki、Sanefuji Masafumi、Akamine Satoshi、Kanno Shunsuke、Ishizaki Yoshito、Torisu Hiroyuki、Kira Ryutaro、Matsumoto Naomichi、Sakai Yasunari、Ohga Shouichi
    • Journal Title

      Brain and Development

      Volume: 41 Issue: 4 Pages: 378-381

    • DOI

      10.1016/j.braindev.2018.10.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed

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Published: 2018-04-23   Modified: 2021-02-19  

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