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Moleculer cell biological and clinical study of hereditary optic neuropathy

Research Project

Project/Area Number 04454447
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionKeio University

Principal Investigator

OGUCHI Yoshihisa  Keio Univ, Medicine, Professor, 医学部, 教授 (70051498)

Co-Investigator(Kenkyū-buntansha) IDEI Takeshi  Keio Univ, Medicine, Instructor, 医学部, 助手 (90223130)
SAGA Masamichi  Keio Univ, Medicine, Instructor, 医学部, 助手 (00245557)
SUZUKI Saburosuke  Keio Univ, Medicine, Assist Professor, 医学部, 講師 (40162945)
KATSURA Hiroshi  Keio Univ, Medicine, Assist Professor, 医学部, 講師 (40129391)
MASHIMA Yukihiko  Keio Univ, Medicine, Assist Professor, 医学部, 講師 (40157186)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1992: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsLeber disease / Mitochondrial DNA / Heterplasmy / 11778 mutation / MRI / VEP / Idebenone / 3460変異 / 14484変異 / 遺伝子治療 / レーベル視神経症 / 点突然変異 / ヘテロプラスミー / 遺伝的異質 / SSCP / PCR
Research Abstract

Japanese patients with Leber's hereditary optic neuropathy(LHON)were investigated as to the genotype of mtDNA mutations.The 11778 mutation were identified in 47 pedigrees, the 14484 mutation in 4 pedigrees, and the 3460 in 3 pedigrees. In Japan, the 11778 mutation was prevalent in LHON patients, which is different from the Caucasian patients. Molecular testing of mtDNA is effective for diagnosis of LHON.Heteroplasmy was found 5 of the 36 pedigrees with the 11778 mutation tested. We develped a new application of quantification of heteroplasmy by PCR-SSCP analysis and individuals wiht less than 60% of mutant mtDNA are probably at lesser risk for developing the disease. The clinical characteristics of the three genotype were similar to those of Caucasian patients. Patients with the 14484 mutation have a high frequency of visual recovery. Yhe results of flash VEP and MRI study revealed that pathogenesis of the optic nerve in the acute stage of LHON was different from that of optic neuritis. Concerning treatment of LHON,there is no effective therapy. However, one young parient recovered vision after treatment with this medicine. Idebenone is one of candidate medicines to be appled for the patients.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Mashima Y,Hiida Y,Oguchi Y: "Remission of Leber´s hereditary optic neuro-pathy with idebenone." Lancet. 340. 368-369 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Hiida Y,Oguchi Y,Kudoh J,Shimizu N: "High mutation frequency at position 11778 in mitochondrial ND4 gene in Japanese families with Leber´s hereditary optic neuropathy." Hum Genet. 92. 101-102 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Hiida Y,Oguchi Y,Kudoh J,Shimizu N: "DNA diagnosis of Leber´s hereditary optic neuropathy using dried blood specimens." Am J Ophthalmol. 116. 773-774 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 篠田啓、緋田芳樹、真島行彦、小口芳久: "ミトコンドリアDNAのnt11778遺伝子変異をもつレ-ベル視神経症16家系の臨床所見" 臨床眼科. 47. 1727-1730 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Saga M,Hiida Y,Oguchi Y,Kudoh J,Shimizu N: "Risk of false-positive DNA diagnosis of Leber´s hereditary optic neuropathy." Am J Ophthalmol. 119. 245-246 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Saga M,Hiida Y,Oguchi Y,Kudoh J,Shimizu N: "Ouantitative determination of heteroplasmy in Leber´s hereditary optic neuropathy by single-strand conformation polymorphism." Invest Ophthalmol Vis Sci. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 小口芳久: "Leber病・臨床DNA診断" 金原(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Hiida Y,Oguchi Y: "Remission of Leber's hereditary optic neuropathy with idebenone." Lancet. 340. 368-369 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Hiida Y,Oguchi Y, Kudoh J,Shimizu N: "High mutation frequency at position 11778 in mitochondrial ND4 gene in Japanese families with Leber's hereditary optic neuropathy." Hum Gent. 92. 101-102 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Hiida Y,Oquchi Y,Kudoh J,Shimizu N: "DNA diagnosis of Leber's hereditary optic neuropathy using dried blood specimens." Am J Ophthalmol. 116. 773-774 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Saga M,Hiida Y,Oguchi Y,Kudon J,Shimizu N: "Risk of false-positive DNA diagnosis of Leber's hereditary optic neuropathy." Am J Ophthalmol. 119. 245-246 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mashima Y,Saga M,Hiida Y,Oguchi Y,Kudoh J,Shimizu N: "Quantitative determination of heteroplasmy in Leber's hereditary optic neuropathy by single-strand conformation polymorphism." Invest Ophthalmol Vis Sci. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Mashima: "Lack of differences among mitochondrial DNA in family members with LHON and differing visual outcomes." Journal of Neuro-ophthalmology. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Mashima: "Risk of false-positive molecular genetic diagnosis of LHON." American Journal of Ophthalmology. 119(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 緋田 芳樹: "ミトコンドリアDNA3460変異を有する日本人レ-ベル視神経症の分子生物学的解析." 日本眼科学会雑誌. (印刷予定). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 真島 行彦: "日本におけるレ-ベル病" 臨床科学. 30. 369-375 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 真島 行彦: "レ-ベル病" 神経眼科. 11. 34-41 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 中西 眞美: "心因性視力障害と診断されたレ-ベル病の2症例" 眼科. 36. 811-814 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y,Mashima: "High frequency of mutations at position 11778 in mtND4 gene in Japanese families with Leber's hereditary optic Neuropathy" Human Genetics. 92. 101-102 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y,Mashima: "DNA diagnosis of Leber's hereditary optic neuropathy by using dried blood specimens" American Journal of Ophthalmology. 116. 773-774 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.MASHIMA: "Remission of Leber's hereditary optic neuropathy with idebenone" Lanset. 340. 368-369 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小田 仁: "40歳以下で発症した両眼性視神経症の予後不良例の検討" 臨床眼科. 46. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 篠田 啓: "ミトコンドリアDNAのnt11778遺伝子変異をもつレーベル視神経症16家系の臨床所見" 臨床眼科. 46. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 恵子: "視力回復を示したnt11778遺伝子変異をもつレーベル視神経症の2家系" 臨床眼科. 46. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.MASHIMA: "A high frequency of mutation at position 11778 in mitochondrial ND4 gene in Japanese families with Leber's hereditary optic neuropathy" Human Genetics. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 小口 芳久: "臨床遺伝医学〔III〕 分子病 5.6レーベル病" 診断と治療社, 643 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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