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Study on ketone body metabolism and its defects: mainly gene expression mechanism of SCOT gene

Research Project

Project/Area Number 24591505
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionGifu University

Principal Investigator

FUKAO Toshiyuki  岐阜大学, 医学(系)研究科(研究院), 教授 (70260578)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsケトン体代謝 / 先天代謝異常症 / スプライシング / 遺伝子異常 / 遺伝子発現調節 / OXCT1 / ChiPアッセイ
Outline of Final Research Achievements

I mainly analyzed the mechanism of liver-specific suppression of SCOT gene.
1)Liver specific suppression activity was not observed in human and mouse 3’non-coding region sequences when examined by a luciferase assay. 2)Using ChiP assay with RNA polymerase 2 antibody, transcriptional activity of SCOT hene regions were compared with that of GAPDH in mouse heart, kidney and liver tissues. SCOT transcription in the liver was much low comparing to that in the kidney and heart. These data suggest that SCOT gene expression is suppressed mainly at the transcriptional level in liver. I also confirmed that a missense mutation c.949G>A(D317N) caused exon 10 skipping in the mini-gene splicing experiment, indicating that this mutation functions as a splicing mutation rather than amissense mutation.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012 2011

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 1 results) Presentation (22 results) (of which Invited: 4 results) Book (1 results)

  • [Journal Article] Application of Multiplex ligation-dependent probe amplification and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two Japanese patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.2015

    • Author(s)
      Aoyama Y, Yamamoto T, Sakaguchi N, Ishige M, Tanaka T, Ichihara T, Ohara K, Kouzan H, Kinosada Y, Fukao T
    • Journal Title

      Int J Mol Med

      Volume: 未定

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inborn errors of ketone body utilization2015

    • Author(s)
      Hori T, Yamaguchi S, Shintaku H, Horikawa R, Shigematsu Y, Hakayanagi M, Fukao T
    • Journal Title

      Pediatr Int

      Volume: 57 Issue: 1 Pages: 51-48

    • DOI

      10.1111/ped.12585

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic encephalopathy in beta-ketothiolase deficiency: The first report from India.2014

    • Author(s)
      Akella RR, Aoyama Y, Mori C, Lingappa L, Cariappa R, Fukao T.
    • Journal Title

      Brain Dev

      Volume: undefiied Issue: 6 Pages: 537-540

    • DOI

      10.1016/j.braindev.2013.07.007

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The first case in Asia of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (HSD10 disease) with atypical presentation.2014

    • Author(s)
      Fukao T, Akiba K, Goto M, Kuwayama N, Morita M, Hori T, Aoyama Y, Venkatesan R, Wierenga R, Moriyama Y, Hashimoto T, Usuda N, Murayama K, Ohtake A, Hasegawa Y, ShigematsuY, Hasegawa Y.
    • Journal Title

      J Hum Genet

      Volume: 59 Issue: 11 Pages: 609-614

    • DOI

      10.1038/jhg.2014.79

    • NAID

      40020269650

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ketone body metabolism and its defects.2014

    • Author(s)
      Fukao T, Mitchell G, Saas JO, Hori T, Orii K, Aoyama Y
    • Journal Title

      J Inherited Metab Dis

      Volume: 37 Issue: 4 Pages: 541-551

    • DOI

      10.1007/s10545-014-9704-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency.2014

    • Author(s)
      Shafqat N, Kavanagh KL, Sass JO, Christensen E, Fukao T, Lee WH, Oppermann U, Yue WW.
    • Journal Title

      J Inherit Metab Dis

      Volume: undefined Issue: 6 Pages: 983-987

    • DOI

      10.1007/s10545-013-9589-z

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A treatable new cause of chorea: beta-ketothiolase deficiency.2013

    • Author(s)
      Buhaş D, Bernard G, Fukao T, Décarie JC, Chouinard S, Mitchell GA
    • Journal Title

      Mov Disord.

      Volume: 28 Issue: 8 Pages: 1054-1056

    • DOI

      10.1002/mds.25538

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of MLPA for Human ACAT1 Gene and Identification of a Heterozygous Alu-mediated Deletion of Exons 2 and 3 in a Patient with Mitochondrial Acetoacetyl-CoA Thiolase (T2) Deficiency.2013

    • Author(s)
      Fukao T, Aoyama Y, Murase K, Hori T, Wierenga R, Boneh A, Kondo N
    • Journal Title

      Mol Genet Metab

      Volume: 110 Issue: 1-2 Pages: 184-187

    • DOI

      10.1016/j.ymgme.2013.07.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular basis of two exon skipping (exons 12 and 13) by c.1248+5g>a in OXCT1 gene. Study on intermediates of OXCT1 transcripts in fibroblasts.2013

    • Author(s)
      Hori T, Fukao T, Murase K, Sakaguchi N, Harding CO, Kondo N.
    • Journal Title

      Hum Mutat

      Volume: 34 Issue: 3 Pages: 473-480

    • DOI

      10.1002/humu.22258

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intracellular in vitro probe acylcarnitine assay for identifying deficiencies ofcarnitine transporter and carnitine palmitoyltransferase-12013

    • Author(s)
      Purevsuren J
    • Journal Title

      Anal Bioanal Chem

      Volume: 405 Issue: 4 Pages: 1345-1351

    • DOI

      10.1007/s00216-012-6532-3

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical and molecular aspects of Japanese children with medium chain acyl-CoA dehydrogenase deficiency2012

    • Author(s)
      Purevsuren J, Fukao T (8/9), Yamaguchi S (9/9), et al
    • Journal Title

      Mol Genet Metab

      Volume: 107 Issue: 1-2 Pages: 237-240

    • DOI

      10.1016/j.ymgme.2012.06.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bezafibrate can be a new treatment option for mitochondrial fatty acid oxidation disorders : Evaluation by in vitro probe acylcarnitine assay2012

    • Author(s)
      Yamaguchi S (1/12), Fukao T (11/12), et al
    • Journal Title

      Mol Genet Metab

      Volume: 107 Issue: 1-2 Pages: 87-91

    • DOI

      10.1016/j.ymgme.2012.07.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three Japanese patients with beta-ketothiolase deficiency whoshare a mutation, c.431A>C(H144P) in ACAT1 : subtle abnormality in urinary organic acid analysis and blood acylvcarnitine analysis using tandem mass spectrometry2011

    • Author(s)
      Fukao T
    • Journal Title

      JIMD Reports

      Volume: 3 Pages: 108-115

    • DOI

      10.1007/8904_2011_72

    • ISBN
      9783642249358, 9783642249365
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Three patients with HSD10 disease in Japan.2015

    • Author(s)
      Fukao T, Sasai H, Aoyama Y,Akiba K, Goto M, Hasegawa Y, Kobayashi M, Ida H, Akagawa S, Hori T,Hasegawa Y, Yamaguchi S, Shigematsu Y.
    • Organizer
      4th Asian Congress for Inherited Metabolic Disease 2015
    • Place of Presentation
      Taipei(Taiwan)
    • Year and Date
      2015-03-20 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] HMG-CoAリアーゼ(HMGCL)遺伝子のMLPA法確立とHMGCL欠損症1症例における Uniparental disomyの同定2014

    • Author(s)
      青山友佳,山本俊至,坂口直美,石毛美夏,田中藤樹,市原朋子,大原克明,深尾敏幸
    • Organizer
      第56回日本先天代謝異常学会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-12 – 2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] ケトン性低血糖発作を契機に診断したHSD10病の4歳男児2014

    • Author(s)
      赤川翔平、保坂泰介、石井紘介、寺口正之、村上貴孝、圀府寺美、木野稔、 深尾敏幸、青山友佳、重松陽介
    • Organizer
      第56回日本先天代謝異常学会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-12 – 2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 本邦初の乳児期発症のHSD10病症例2014

    • Author(s)
      小林正久,深尾敏幸,重松陽介,長谷川有紀,村山圭,井田博幸
    • Organizer
      第56回日本先天代謝異常学会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-12 – 2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] ACAT1遺伝子のイントロン9へのAlu挿入はエクソン10の認識に影響を与える。2014

    • Author(s)
      深尾敏幸、堀友博、笹井英雄、大塚博樹、青山友佳
    • Organizer
      第56回日本先天代謝異常学会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-12 – 2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミトコンドリアHMG-CoA合成酵素欠損症の急性期症状2014

    • Author(s)
      伊藤哲哉 中島葉子 加藤沙耶香 深尾敏幸
    • Organizer
      第56回日本先天代謝異常学会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-12 – 2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Clinical Importance of ketone body metabolism and its defects.2014

    • Author(s)
      Fukao T
    • Organizer
      International Conference on Inborn Errors of Metabolism and 3rd National Conference of ISIEM
    • Place of Presentation
      Hyderabad (India)
    • Year and Date
      2014-09-19 – 2014-09-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The first case in Asia of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (HSD10 disease) without intellectual disability.2014

    • Author(s)
      Akiba K, Fukao T, Goto M, kuwayama N, Morita M, Hori T, Aoyama Y, Venkatesan R, Wierenga R, Moriyama Y, Hashimoto T, Usuda N, Murayama K, Ohtake T, Hasegawa Y, Shigematsu Y, Hasegawa Y
    • Organizer
      Annual symposium of the society for the study of inborn erroros of metabolism
    • Place of Presentation
      Innsbruck (Austria)
    • Year and Date
      2014-09-02 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Alu elements insertions into intron 9 affect exon 10 recognition with a suboptimal splice acceptor site in human ACAT1 gene.2014

    • Author(s)
      Fukao T, Hori T, Sasai H, Ohtsuka H, Kimura T, Aoyama Y
    • Organizer
      Annual symposium of the society for the study of inborn errors of metabolism
    • Place of Presentation
      Innsbruck(Austria)
    • Year and Date
      2014-09-02 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] ケトン体代謝異常症と急性脳症2013

    • Author(s)
      深尾敏幸
    • Organizer
      第18回日本神経感染症学会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Ketone body metabolism and its defects. Update.2013

    • Author(s)
      Fukao T.
    • Organizer
      12th International Congress of Inborn Errors of Metabolism
    • Place of Presentation
      Barcelona
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] (Educational lecture) Inborn errors of ketogenesis and ketone body utilization2013

    • Author(s)
      Fukao T
    • Organizer
      The 55th Annual meeting of the Japanese Society for Inherited Metabolic Diseases
    • Place of Presentation
      幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] HMG-CoAリアーゼ欠損症のMPLA法の確立と1症例におけるエクソン2-4を含む欠失の同定2013

    • Author(s)
      青山 友佳, 石毛 美夏,田中 藤樹,深尾 敏幸
    • Organizer
      第40回日本マススクリーニング学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] 日本初のHSD10病(2-methyl-3-hydroxybutryl-CoA 脱水素酵素欠損症)の報告2013

    • Author(s)
      深尾敏幸, 秋葉和壽, 桑山信希, 森田実喜子, 青山友佳、後藤正博, Venkatesan Rajaran, Rikkert Wierenga、臼田信光、森山陽介、重松陽介、長谷川有紀、大竹明、村山圭、堀友博、長谷川行洋
    • Organizer
      第58回日本人類遺伝学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] The first case of HSD10 disease (2-Methyl-3-Hydroxybutyryl-CoA dehydrogenase deficiency) from Asia2013

    • Author(s)
      Fukao T, Akiba K, Goto M, Kuwayama N, Morita M, Hori T, Aoyama Y, Venkatesan R, Wierenga R, Hasegawa Y, Shigematsu Y, Ohtake A, Moriyama Y, Usuda N, Hasegawa Y
    • Organizer
      The 3rd Asian Congress for Inherited Metabolic Diseases / The 55th Annual meeting of the Japanese Society for Inherited Metabolic Diseases
    • Place of Presentation
      幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] An Exonic splicing enhancer mutation indetified in German beta-ketothiolase deficient patients.2012

    • Author(s)
      Fukao T, Sass JO, Konstantopoulou V, Marquardt T, Frauendienst-Egger G, Kondo N.
    • Organizer
      Annual symposium of Society for the Study of Inborn Errors of Metabolism.
    • Place of Presentation
      Birmingham, UK
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular basis of two exon skipping (exons 12 and 13) by c. 1248+5G>A in fibroblasts from a SCOT deficient patient. Study of splicing order in SCOT transcripts in fibroblasts from controls and the patient.2012

    • Author(s)
      Hori T, Fukao T, Harding CO, Kondo N.
    • Organizer
      Annual symposium of Society for the Study of Inborn Errors of Metabolism.
    • Place of Presentation
      Birmingham, UK
    • Related Report
      2012 Research-status Report
  • [Presentation] ケトン体代謝異常症の病態解明に関する研究2012

    • Author(s)
      深尾敏幸
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 新生児期に診断され,良好な経過を示している3-ヒドロキシ3-メチルグルタル酸血症の1例.2012

    • Author(s)
      大倉絵梨,長沼邦明,中田節子,萩元緑朗,佐野葉子,多田明良,山口清次,長谷川有紀,小林弘典,深尾敏幸
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] 躁病様行動にバルプロ酸が有効であった移植後思春期大脳型副腎白質ジストロフィーの1例2012

    • Author(s)
      小関道夫,神田香織,川本典生,折居建治,加藤善一郎,深尾敏幸,近藤直実,下澤伸行,鈴木康之,植木啓文
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] 新生児期にGA2と診断され,生後5か月よりBEZ投与を開始した二絨毛膜二羊膜双胎例2012

    • Author(s)
      大塚博樹,深尾敏幸,森本将敬,折居建治,山田健治,小林弘典,長谷川有紀,山口清次,近藤直実
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] 新生児期に発症したミトコンドリア呼吸鎖異常症の1例2012

    • Author(s)
      森本将敬,深尾敏幸,折居建治,寺本貴英,松井永子,加藤善一郎,大竹明,村山圭,高柳正樹,近藤直実
    • Organizer
      第54回日本先天代謝異常学会総会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Book] タンデムマス・スクリーニングガイドブック2013

    • Author(s)
      深尾敏幸
    • Publisher
      診断と治療社
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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