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Identification of novel disease genes and analysis of their molecular functions in progressive familial intrahepatic cholestasis

Research Project

Project/Area Number 17K16240
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionUniversity of Tsukuba

Principal Investigator

Imagawa Kazuo  筑波大学, 医学医療系, 講師 (40708509)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords胆汁うっ滞 / 遺伝性肝疾患 / エクソーム / 小児 / 肝疾患 / 小児肝疾患 / 遺伝性疾患
Outline of Final Research Achievements

In this study, we conducted a comprehensive genetic analysis using a next-generation sequencer for neonatal-onset bile stasis of unknown aetiology, and found cases that were difficult to diagnose by analysis of known disease-related genes. We obtained basic data for further analysis using comprehensive exploratory methods such as exome analysis, transcriptome analysis using liver tissue, and methylome analysis. In addition, we performed molecular functional analysis of gene mutations found in a case of progressive familial intrahepatic cholestasis to evaluate the pathogenesis in vitro and to evaluate the efficacy of small molecules.

Academic Significance and Societal Importance of the Research Achievements

新生児乳児期発症の原因不明胆汁うっ滞症の中には未だ疾患と関連する遺伝子異常が同定されず、今後新規疾患概念の確立に寄与できる集団が含まれていることが明らかになった。今後の胆汁うっ滞病態の分子機序を考察するうえで重要な基礎データが得られた。今後は未診断患者の一群から新規疾患の発見が期待できる。また、日本で最も多く検出されたABCB11変異について、分子機能解析を実施し、病態と新規薬剤の薬効評価を行い、将来の分子機序を基礎とした治療応用への展開も期待される結果が得られた。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] An Adult Patient with Alagille Syndrome Showing Mainly Renal Failure and Vascular Abnormality without Liver Manifestation2020

    • Author(s)
      Shimohata Homare、Imagawa Kazuo、Yamashita Marina、Ohgi Kentaro、Maruyama Hiroshi、Takayasu Mamiko、Hirayama Kouichi、Kobayashi Masaki
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 22 Pages: 2907-2910

    • DOI

      10.2169/internalmedicine.4780-20

    • NAID

      130007939944

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-11-15
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proposal of a liver histology‐based scoring system for bile salt export pump deficiency2020

    • Author(s)
      Zen Yoh、Kondou Hiroki、Nakazawa Atsuko、Tanikawa Ken、Hasegawa Yasuhiro、Bessho Kazuhiko、Imagawa Kazuo、Ishige Takashi、Inui Ayano、Suzuki Mitsuyoshi、Kasahara Mureo、Yamamoto Kouji、Yoshioka Takako、Kage Masayoshi、Hayashi Hisamitsu
    • Journal Title

      Hepatology Research

      Volume: Online ahead of print. Issue: 6 Pages: 754-762

    • DOI

      10.1111/hepr.13494

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A case of autism spectrum disorder with cleft lip and palate carrying a mutation in exon 8 of AUTS22019

    • Author(s)
      Saeki Saki、Enokizono Takashi、Imagawa Kazuo、Fukushima Hiroko、Kajikawa Daigo、Sakai Aiko、Tanaka Mai、Ohto Tatsuyuki、Suzuki Hisato、Uehara Tomoko、Takenouchi Toshiki、Kenjiro Kosaki、Takada Hidetoshi
    • Journal Title

      Clinical Case Reports

      Volume: 7 Issue: 11 Pages: 2059-2063

    • DOI

      10.1002/ccr3.2377

    • NAID

      120007127802

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel missense PTEN mutation identified in a patient with macrocephaly and developmental delay2019

    • Author(s)
      Ueno Yuichi、Enokizono Takashi、Fukushima Hiroko、Ohto Tatsuyuki、Imagawa Kazuo、Tanaka Mai、Sakai Aiko、Suzuki Hisato、Uehara Tomoko、Takenouchi Toshiki、Kosaki Kenjiro、Takada Hidetoshi
    • Journal Title

      Human Genome Variation

      Volume: 6 Issue: 1 Pages: 25-25

    • DOI

      10.1038/s41439-019-0056-8

    • NAID

      120007127824

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis.2018

    • Author(s)
      Imagawa K, Hayashi H, Sabu Y, Tanikawa K, Fujishiro J, Kajikawa D, Wada H, Kudo T, Kage M, Kusuhara H, Sumazaki R.
    • Journal Title

      J Hum Genet.

      Volume: 印刷中 Issue: 5 Pages: 569-577

    • DOI

      10.1038/s10038-018-0431-1

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interinstitutional patient transfers between rapid chemotherapy cycles were feasible to utilize proton beam therapy for pediatric Ewing sarcoma family of tumors.2018

    • Author(s)
      Nakao T, Fukushima H, Fukushima T, Suzuki R, Hosaka S, Yamaki Y, Kobayashi C, Iwabuchi A, Imagawa K, Sakai A, Shinkai T, Masumoto K, Sakashita S, Masumoto T, Mizumoto M, Sumazaki R, Sakurai H
    • Journal Title

      Reports of Practical Oncology and Radiotherapy

      Volume: 23 Issue: 5 Pages: 442-450

    • DOI

      10.1016/j.rpor.2018.08.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Schuurs-Hoeijmakers syndrome in two patients from Japan2018

    • Author(s)
      Hoshino Yusuke、Enokizono Takashi、Imagawa Kazuo、Tanaka Ryuta、Suzuki Hisato、Fukushima Hiroko、Arai Junichi、Sumazaki Ryo、Uehara Tomoko、Takenouchi Toshiki、Kosaki Kenjiro
    • Journal Title

      American Journal of Medical Genetics Part A

      Volume: 179 Issue: 3 Pages: 341-343

    • DOI

      10.1002/ajmg.a.9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【小児疾患の診断治療基準】(第2部) 疾患 消化器疾患 新生児肝炎症候群2018

    • Author(s)
      今川 和生
    • Journal Title

      小児内科

      Volume: 50 Pages: 442-443

    • Related Report
      2018 Research-status Report
  • [Journal Article] 指定難病最前線 vol. 74 アラジール症候群2018

    • Author(s)
      今川 和生、和田宏来、田川学、須磨崎亮
    • Journal Title

      新薬と臨床

      Volume: 67 Pages: 1572-1576

    • Related Report
      2018 Research-status Report
  • [Presentation] Congenital biliary dilatation in an infant with citrin deficiency2020

    • Author(s)
      Morita A, Imagawa K, Tagawa M, Takada H
    • Organizer
      The 6th World Congress of Pediatric Gastroenterology, Hepatology and Nutrition
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alagille症候群における肝外合併症2020

    • Author(s)
      今川 和生、森田篤志、田川学、須磨崎亮
    • Organizer
      第24回日本肝臓学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝疾患における移行期医療 Alagille症候群など遺伝性胆汁うっ滞疾患における進学時期と移行期医療2020

    • Author(s)
      今川 和生, 森田 篤志, 田川 学
    • Organizer
      第56回日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 子どもの難病とともに生きる-患者会の取り組み-「乳児黄疸ネット」を活用した希少難治性肝疾患の診断支援と情報発信2019

    • Author(s)
      今川 和生
    • Organizer
      第46回日本小児栄養消化器肝臓学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小児肝疾患の移行期医療:現状と問題点 Alagille症候群の成人期診療に関する全国調査2019

    • Author(s)
      今川 和生, 佐々木 英之, 田中 篤
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 胆汁うっ滞を伴うNiemann-Pick病C型の乳児例における尿中胆汁酸分析の有用性2019

    • Author(s)
      今川 和生、成田 綾、森田 篤志、田川 学、中野 聡、成高 中之、武井 一、入戸野 博、高田 英俊
    • Organizer
      第61回日本先天代謝異常学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新生児・乳児胆汁うっ滞疾患と遺伝学的検査・診断の最前線2019

    • Author(s)
      戸川 貴夫、伊藤 彰悟、伊藤 孝一、杉浦 時雄、今川 和生、林 久允、阿久津 英憲、齋藤 伸治
    • Organizer
      第64回日本人類遺伝学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 乳児胆汁うっ滞性疾患 ~乳児黄疸ネットを活用した診断支援~2018

    • Author(s)
      今川和生
    • Organizer
      第117回茨城小児科学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 新生児・乳児の胆汁うっ滞性疾患を効率よく診断するための乳児黄疸ネット2018

    • Author(s)
      今川 和生, 戸川 貴夫, 伊藤 彰悟,遠藤 剛
    • Organizer
      第63回日本新生児成育医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 進行性家族性肝内胆汁うっ滞症2型乳児の臨床像と胆汁酸トランスポーターBSEPの変異機能解析2018

    • Author(s)
      今川 和生, 林 久允, 谷川 健, 和田 宏来, 工藤 豊一郎, 鹿毛 政義, 須磨崎 亮
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 本邦の進行性家族性肝内胆汁うっ滞症2型で頻度の多いABCB11 C129Y変異の機能解析2018

    • Author(s)
      今川 和生, 林 久允, 佐分 雄祐, 伊藤 彰悟, 戸川 貴夫, 高田 英俊
    • Organizer
      第35回日本小児肝臓研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 希少難治肝疾患の臨床研究を推進する上での乳児黄疸ネットの活用2017

    • Author(s)
      今川 和生, 田川 学, 酒井 愛子, 須磨崎 亮
    • Organizer
      第120回日本小児科学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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