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2022 Fiscal Year Annual Research Report

希少遺伝子疾患の新規遺伝子同定と治療戦略を見据えた病態解析

Research Project

Project/Area Number 22H03047
Allocation TypeSingle-year Grants
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

三宅 紀子  国立研究開発法人国立国際医療研究センター, 研究所, 疾患ゲノム研究部 部長 (40523494)

Project Period (FY) 2022-04-01 – 2025-03-31
Keywords網羅的ゲノム解析 / 病的バリアント / 単一遺伝子疾患
Outline of Annual Research Achievements

希少遺伝性疾患の症例収集については、協力医療機関も増え10施設からの検体提供が得られており昨年度1年間で89症例(患者のみで)を新規にリクルートすることができた。発端者を対象に、主に全エクソーム解析を行った。解析パイプラインも最新のアノテーションの付加や、コピー数解析等の解析フローも改良した。解析症例の中から、繰り返す感染症を呈する兄弟例の解析により新規の疾患遺伝子候補が同定され、現在機能解析を行い、病態発症のメカニズムを解析中である。その外にも世界でまだ数例しか報告されていない新規の希少遺伝子疾患の病的バリアントを同定し、現在3報の症例報告論文を投稿・作成中である。また、他施設との共同研究として、自閉症(Miyake et al., 2023, Eur J Hum Genet)、てんかん(Acta Neuropathol Commun. 2023), Cockayne症候群(Aging, 2022、Hum Genome Var. 2022), 短肢性小人症(Clin Genet. 2022)、小脳低形成・萎縮症(Genet Med. 2022)、知的障害(Hum Genome Var. 2022)のゲノム解析を行い、病的バリアントを同定し、学術論文として発表した。中でも自閉症の解析では、405症例(351 trio, 24 quads, 2 quitets)に対し全エクソーム解析を行い、53症例に症状を説明できる候補バリアント(single nucleotide variants/ small indels)を同定した。さらに、コピー数解析を行い、13症例において症状を説明できる病的コピー数変化を同定した。分子診断率は66/405(16.3%) なり、これは既報より少し高い結果であった。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

予定数よりも多い症例数の集積があり、順次網羅的ゲノム解析を進められている。また少しずつ協力医療機関を増やすことができており、今後も症例集積が期待できる。

Strategy for Future Research Activity

現在行っている症例収集・網羅的ゲノム解析を継続し、新規疾患遺伝子候補に関しては積極的に機能解析、国際共同研究を進め、新規疾患遺伝子の同定および病態解明を行う。既知の疾患遺伝子のバリアントであっても、新規のバリアントや臨床症状に特徴がある症例に等に関しては、科学的に新しい知見がある場合には積極的に発表する。国内外での発表を積極的に行い、多施設共同研究を進める。

  • Research Products

    (28 results)

All 2023 2022 Other

All Int'l Joint Research (6 results) Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 15 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results)

  • [Int'l Joint Research] Genetic Health Service New Zealand/University of Auckland, Auckland(ニュージーランド)

    • Country Name
      NEW ZEALAND
    • Counterpart Institution
      Genetic Health Service New Zealand/University of Auckland, Auckland
  • [Int'l Joint Research] Tel Aviv University/The Genetics Institute(イスラエル)

    • Country Name
      ISRAEL
    • Counterpart Institution
      Tel Aviv University/The Genetics Institute
  • [Int'l Joint Research] Hospital Kuala Lumpur(マレーシア)

    • Country Name
      MALAYSIA
    • Counterpart Institution
      Hospital Kuala Lumpur
  • [Int'l Joint Research] Vietnam Academy of Science and Tech/Vietnam National Children's Hospital(ベトナム)

    • Country Name
      VIET NAM
    • Counterpart Institution
      Vietnam Academy of Science and Tech/Vietnam National Children's Hospital
  • [Int'l Joint Research] Friedrich-Baur-Institute(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      Friedrich-Baur-Institute
  • [Int'l Joint Research]

    • # of Other Countries
      12
  • [Journal Article] Molecular diagnosis of 405 individuals with autism spectrum disorder2023

    • Author(s)
      Miyake Noriko、Tsurusaki Yoshinori、Fukai Ryoko et al.
    • Journal Title

      European Journal of Human Genetics

      Volume: - Pages: -

    • DOI

      10.1038/s41431-023-01335-7

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An integrated genetic analysis of epileptogenic brain malformed lesions2023

    • Author(s)
      Fujita Atsushi、Kato Mitsuhiro、Sugano Hidenori、Iimura Yasushi、others、Miyake Noriko、Kakita Akiyoshi、Matsumoto Naomichi
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 11 Pages: 33

    • DOI

      10.1186/s40478-023-01532-x

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel NONO variant that causes developmental delay and cardiac phenotypes2023

    • Author(s)
      Itai Toshiyuki、Sugie Atsushi、Nitta Yohei、others、Miyake Noriko、Misawa Kazuharu、Mizuguchi Takeshi、Miyatake Satoko、Matsumoto Naomichi
    • Journal Title

      Scientific Reports

      Volume: 13 Pages: 975

    • DOI

      10.1038/s41598-023-27770-6

    • Peer Reviewed
  • [Journal Article] Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42?affected individuals2023

    • Author(s)
      Saida Ken、Maroofian Reza、others、Miyake Noriko、others、Matsumoto Naomichi
    • Journal Title

      Genetics in Medicine

      Volume: 25 Pages: 90~102

    • DOI

      10.1016/j.gim.2022.09.010

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Three <scp>KINSSHIP</scp> syndrome patients with mosaic and germline <scp> <i>AFF3</i> </scp> variants2023

    • Author(s)
      Inoue Yuta、Tsuchida Naomi、Okamoto Nobuhiko、Shuichi Shimakawa、Ohashi Kei、Saitoh Shinji、Ogawa Atsushi、Hamada Keisuke、Sakamoto Masamune、Miyake Noriko、Hamanaka Kohei、Fujita Atsushi、Koshimizu Eriko、Miyatake Satoko、Mizuguchi Takeshi、Ogata Kazuhiro、Uchiyama Yuri、Matsumoto Naomichi
    • Journal Title

      Clinical Genetics

      Volume: 103 Pages: 590~595

    • DOI

      10.1111/cge.14292

    • Peer Reviewed
  • [Journal Article] Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy2022

    • Author(s)
      Sakamoto Masamune、Iwama Kazuhiro、Sasaki Masayuki、others、Miyake Noriko、Matsumoto Naomichi
    • Journal Title

      Genetics in Medicine

      Volume: 24 Pages: 2453~2463

    • DOI

      10.1016/j.gim.2022.08.007

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Distal 2q duplication in a patient with intellectual disability2022

    • Author(s)
      Suzuki Toshifumi、Osaka Hitoshi、Miyake Noriko、Fujita Atsushi、Uchiyama Yuri、Seyama Rie、Koshimizu Eriko、Miyatake Satoko、Mizuguchi Takeshi、Takeda Satoru、Matsumoto Naomichi
    • Journal Title

      Human Genome Variation

      Volume: 9 Pages: 39

    • DOI

      10.1038/s41439-022-00215-8

    • Peer Reviewed
  • [Journal Article] Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease?like Vascular Formation Associated With <i>RNF213</i> p.R4810K Variant2022

    • Author(s)
      Ikeuchi Yasuhito、Kitayama Jiro、Sahara Noriyuki、Okata Takuya、Miyake Noriko、Matsumoto Naomichi、Kitazono Takanari、Ago Tetsuro
    • Journal Title

      Neurology Genetics

      Volume: 8 Pages: e200017~e200017

    • DOI

      10.1212/NXG.0000000000200017

    • Peer Reviewed
  • [Journal Article] Cockayne syndrome without UV-sensitivity in Vietnamese siblings with novel ERCC8 variants2022

    • Author(s)
      Duong Nguyen Thuy、Dinh Tran Huu、M?hl Britta S.、Hintze Stefan、Quynh Do Hai、Ha Duong Thi Thu、Ngoc Ngo Diem、Dung Vu Chi、Miyake Noriko、Hai Nong Van、Matsumoto Naomichi、Meinke Peter
    • Journal Title

      Aging

      Volume: 14 Pages: 5299~5310

    • DOI

      10.18632/aging.204139

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exome sequencing analysis of Japanese autism spectrum disorder case-control sample supports an increased burden of synaptic function-related genes2022

    • Author(s)
      Kimura Hiroki、Nakatochi Masahiro、Aleksic Branko、Guevara James、Toyama Miho、Hayashi Yu、Kato Hidekazu、Kushima Itaru、Morikawa Mako、Ishizuka Kanako、Okada Takashi、Tsurusaki Yoshinori、Fujita Atsushi、Miyake Noriko、Ogi Tomoo、Takata Atsushi、Matsumoto Naomichi、Buxbaum Joseph、Ozaki Norio、Sebat Jonathan
    • Journal Title

      Translational Psychiatry

      Volume: 12 Pages: 265

    • DOI

      10.1038/s41398-022-02033-6

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] De novo heterozygous variants in <i>KIF5B</i> cause kyphomelic dysplasia2022

    • Author(s)
      Itai Toshiyuki、Wang Zheng、Nishimura Gen、others、Miyake Noriko、Matsumoto Naomichi、Ikegawa Shiro
    • Journal Title

      Clinical Genetics

      Volume: 102 Pages: 3~11

    • DOI

      10.1111/cge.14133

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome2022

    • Author(s)
      Miyatake Satoko、Yoshida Kunihiro、others、Miyake Noriko、Shimohata Takayoshi、Tanaka Fumiaki、Mizuguchi Takeshi、Matsumoto Naomichi
    • Journal Title

      Brain

      Volume: 145 Pages: 1139~1150

    • DOI

      10.1093/brain/awab363

    • Peer Reviewed
  • [Journal Article] Monogenic causes of pigmentary mosaicism2022

    • Author(s)
      Saida Ken、Chong Pin Fee、Yamaguchi Asuka、others、Miyake Noriko、Kato Mitsuhiro、Kira Ryutaro、Matsumoto Naomichi
    • Journal Title

      Human Genetics

      Volume: 141 Pages: 1771~1784

    • DOI

      10.1007/s00439-022-02437-w

    • Peer Reviewed
  • [Journal Article] A rare homozygous missense mutation of COL7A1 in a Vietnamese family2022

    • Author(s)
      Duong Nguyen Thuy、Anh Luong Thi Lan、Sau Nguyen Huu、Anh Nguyen Bao、Miyake Noriko、Van Hai Nong、Matsumoto Naomichi
    • Journal Title

      Human Genome Variation

      Volume: 9 Pages: 13

    • DOI

      10.1038/s41439-022-00192-y

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Whole-exome sequencing revealed a novel ERCC6 variant in a Vietnamese patient with Cockayne syndrome2022

    • Author(s)
      Duong Nguyen Thuy、Anh Nguyen Phuong、Bac Nguyen Duy、Quang Le Bach、Miyake Noriko、Van Hai Nong、Matsumoto Naomichi
    • Journal Title

      Human Genome Variation

      Volume: 9 Pages: 21

    • DOI

      10.1038/s41439-022-00200-1

    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 単一遺伝子疾患の 分子生物学的理解2022

    • Author(s)
      三宅紀子
    • Organizer
      日本人類遺伝学会 第67 回大会
    • Invited
  • [Presentation] Unrevealing the pathomechanism of human monogenic diseases2022

    • Author(s)
      Noriko Miyake
    • Organizer
      第45回日本分子生物学会
    • Invited
  • [Presentation] 転写制御とヒト単一遺伝子疾患2022

    • Author(s)
      三宅紀子
    • Organizer
      第45回日本分子生物学会
    • Invited
  • [Presentation] 先天性疾患のゲノム解析2022

    • Author(s)
      三宅紀子
    • Organizer
      New Insights of Molecular Genetics on Growth Disorders 2022
    • Invited
  • [Presentation] 分子遺伝学から迫る整形外科領域疾患の理解2022

    • Author(s)
      三宅紀子
    • Organizer
      BioSpine Japan The 3rd Meeting
    • Invited
  • [Presentation] Gene identification for Human Mendelian diseases2022

    • Author(s)
      Noriko Miyake
    • Organizer
      Academic seminar of foreign experts
    • Int'l Joint Research / Invited
  • [Presentation] ゲノム解析で見えてきた神経疾患の成り立ち2022

    • Author(s)
      三宅紀子
    • Organizer
      第64回日本小児神経学会学術集会
    • Invited

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Published: 2023-12-25  

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