Development of the biomarker for th e clinical diagnosis of Diamond-Blackfan Anemia

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: HAMAGUCHI Isao 国立感染症研究所, 血液・安全性研究部, 部長 (90348780)
• Project Period (FY): 2009 – 2011
• Keywords: 先天性赤芽球癆 / バイオマーカー / リボソームタンパク質 / アレル欠失

Research Abstract

Some of Diamond-Blackfan anemia(DBA) patients possess mutations in genes coding for ribosomal proteins(RPs). To identify new mutations, we investigated large deletions in the Ribosomal Protein genes. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients possessing mutations that were not detected by sequencing. All patients with a large deletion had a growth retardation phenotype. Our study data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes and biomarker of severe phenotype.

Research Products

• [Journal Article] Extensive gene deletions in Japanese patients with Diamond. Blackfan anemia (2012)
  • Author(s): Kuramitsu M, Sato-Otsubo A, Morio T, Takagi M, Toki T, Terui K, Wang R, Kanno H, Ohga S, Ohara A, Kojima S, Kitoh T, Goi K, Kudo K, Matsubayashi T, Mizue N, Ozeki M, Masumi A, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E, and Hamaguchi I
  • Journal Title: Blood Volume: 119 Pages: 2376-2384
  • Peer Reviewed
• [Journal Article] Ribosomal proteinと造血障害 (2010)
  • Author(s): 浜口功
  • Journal Title: 臨床血液 Volume: 第51巻8号 Pages: 638-645
  • Peer Reviewed
• [Journal Article] 倉光球: Diamond-Blackfan貧血の分子異常 (2010)
  • Author(s): 浜口功
  • Journal Title: 細胞 Volume: 第42巻7号 Pages: 16-19
• [Presentation] Extensive gene deletions in Japanese patients with Diamond Blackfan anemia (2011)
  • Author(s): Kuramitsu M, Matsubara A, Morio T, Takagi M, Toki T, Terui K, Wang R, Kanno H, Ohga S, Ohara A, Masumi A, Momose H, Mizukami T, Takizawa K, Yamaguchi K, Ogawa S, Ito E, Hamaguchi I
  • Organizer: 第73回日本血液学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] New Determination Method for Extensive Gene Deletions in Diamond-Blackfan Anemia (2010)
  • Author(s): Kuramitsu M, Morio T, Takagi M, Toki T, Terui K, Wang R, Masumi A, Mizukami T, Momose H, Takizawa K, Yamaguchi K, Ito E, Hamaguchi I
  • Organizer: 52^<nd> ASH^[(R)] Annual Meeting and Exposition
  • Place of Presentation: Orlando
  • Year and Date: 2010-12-07
• [Presentation] Deficiency of Ribosomal protein associated with Diamond Blackfan anemia induces autophagy (2010)
  • Author(s): Kuramitsu K, Kasai M, Masumi A, Mizukami T, Momose H, Takizawa K, Yamaguchi K, Hamaguchi I
  • Organizer: 第72回日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] A novel method to analyze genomic copy number of Diamond Blackfan anemia responsible genes (2010)
  • Author(s): Kuramitsu M, Morio T, Takagi M, Ozeki M, Masumi A, Mizukami T, Momose H, Takizawa K, Etsuro I, Yamaguchi K, Hamaguchi I
  • Organizer: 第72回日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Ribosomal proteinと造血障害 (2009)
  • Author(s): 浜口功
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] 先天性赤芽球癆(Diamond blackfan anemia)原因遺伝子によるオートファジー活性化の解析 (2009)
  • Author(s): 倉光球、水上拓郎、益見厚子、百瀬暖佳、滝沢和也、笠井道行、山口一成、浜口功
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Book] Diamond-Blackfan貧血におけるリボゾーム機能異常、血液診療エキスパート (2010)
  • Author(s): 倉光球、浜口功
  • Total Pages: 212-214
  • Publisher: 中外医学社
• [Remarks] 国立感染症研究所ホームページ
  • URL: http://www.nih.go.jp/niid/ja/basic-science.html