Analysis of pathogenesis mechanism and development of new treatment in bone marrow failure due to mutation of telomere regulated genes.

• Project/Area Number: 19591141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Nippon Medical School
• Principal Investigator: YAMAGUCHI Hiroki Nippon Medical School, 医学部, 助教 (90297937)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: Dyskeratosis congenita / human telomerase RNA gene / Telomerase reverse transcriptase subunit gene / SBDS gene / TINF2 gene / Mutation / Telomere length / Bone marrow failure / Born marrow failure / telomerase reverse transcriptase subunit gene / telomere length / mutation / polymorphisms

Research Abstract

テロメラーゼ複合体を構成するTERCやTERTなどの変異が再生不良性貧血(AA)などの骨髄不全症(BMF)の約3%に存在する。これらの変異の多くは、haploinsufficiency効果によりテロメラーゼ活性を障害しBMFを発症させる。そこで本邦の成人BMF120人におけるテロメア制御遺伝子変異の検索を行った。結果はTERCの変異を1例、Shelterin複合体を構成するTINF2の変異を3例発見した。本邦におけるテロメア制御遺伝子変異をもつBMFの存在を明らかにした。

Research Products

• [Journal Article] Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes (2008)
  • Author(s): Takeuchi J, Ly H, Yamaguchi H, Carroll KA, Kosaka F, Sawaguchi K, Mitamura Y, Watanabe A, Gomi S, Inokuchi K, Dan K
  • Journal Title: Blood Cells Mol Dis. 40 (2) Pages: 185-91
• [Journal Article] テロメア異常と骨髄不全症 (2008)
  • Author(s): 山口博樹
  • Journal Title: 日本臨床 66 Pages: 483-489
• [Journal Article] 再生不良性貧血の分子病態 (2008)
  • Author(s): 山口博樹, 猪口孝一
  • Journal Title: 血液・腫瘍科 56 Pages: 155-161
• [Journal Article] Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes. (2008)
  • Author(s): Takeuchi J^*, Ly H^*, Yamaguchi H
  • Journal Title: Blood Cells Mol Dis. 40 Pages: 185-91
  • Peer Reviewed
• [Journal Article] Mutations of telomerase complex genes linked to bone marrow failures (2007)
  • Author(s): Yamaguchi H.
  • Journal Title: J Nippon Med Sch. 74 (3) Pages: 202-9
  • NAID: 130004057301
• [Journal Article] 再生不良性貧血のゲノム解析 (2007)
  • Author(s): 山口博樹
  • Journal Title: 分子細胞治療 6 Pages: 467-471
• [Journal Article] Mutations of telomerase complex genes linked to bone marrow failures (2007)
  • Author(s): Yamaguchi H
  • Journal Title: J Nippon Med Sch 74 Pages: 202-9
  • NAID: 130004057301
  • Peer Reviewed
• [Presentation] 本邦の骨髄不全症におけるSBDS遺伝子異常の検索 (2008)
  • Author(s): 山口博樹, 竹内純子, 玉井勇人, 三田村佳勇, 小坂文子, 長谷川節雄, 檀和夫, 猪口孝一
  • Organizer: 第70回日本血液学会
  • Place of Presentation: 京都