Molecular and functional analyses of OTX2 in patients with congenital pituitary hormone deficiency

• Project/Area Number: 21791025
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: DATEKI Sumito 独立行政法人国立成育医療研究センター, 分子内分泌研究部, 共同研究員 (70462801)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 遺伝子 / 転写因子 / 下垂体

Research Abstract

Recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function. In this study, we performed clinical and molecular analyses in patients with OTX2 mutations, and revealed detailed pituitary phenotype of the mutation positive patients and the mechanism of OTX2 for development of hypopituitarism. These results allow for an appropriate hormone-replacement therapy in patients with OTX2 mutations and an understanding of molecular mechanism of pituitary development.

Research Products

• [Journal Article] OTX2遺伝子異常症の臨床的、分子遺伝学的解析 (2010)
  • Author(s): 伊達木澄人、深見真紀、室谷浩二、安達昌功、小坂喜太郎、長谷川高誠、田中弘之、田島敏広、本村克明、木下英一、森内浩幸、緒方勤
  • Journal Title: ホルモンと臨床 57巻 Pages: 987-992
• [Journal Article] Mutation and Gene Copy Number Analyses of Six Pituitary Transcription Factor Genes in 71 Patients with Combined Pituitary Hormone Deficiency : Identification of a Single Patient with LHX4 Deletion. (2010)
  • Author(s): Dateki S, Fukami M, Uematsu A, Kaji M, Iso M, Ono M, Mizota M, Yokoya S, Motomura K, Kinoshita E, Moriuchi H, Ogata T.
  • Journal Title: J Clin Endocrinol Metab 95巻 Pages: 4043-4047
  • Peer Reviewed
• [Journal Article] Heterozygous OTX2 mutations are associated with variable pituitary phenotype. (2010)
  • Author(s): Dateki S, Kosaka K, Hasegawa K, Tanaka H, Azuma N, Yokoya S, Muroya K, Adachi M, Tajima T, Motomura K, Kinoshita E, Moriuchi H, Sato N, Fukami M, Ogata T.
  • Journal Title: J Clin Endocrinol Metab 95巻 Pages: 756-764
  • Peer Reviewed
• [Journal Article] A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency. (2010)
  • Author(s): Ashkenazi-Hoffnung L, Lebenthal Y, Wyatt AW, Ragge NK, Dateki S, Fukami M, Ogata T, Phillip M, Gat-Yablonski G.
  • Journal Title: Hum Genet. 127巻 Pages: 721-729
  • Peer Reviewed
• [Journal Article] Heterozygous OTX2 mutations are associated with variable pituitary phenotype. (2010)
  • Author(s): Dateki S, et al.
  • Journal Title: Journal of Clinical Endocrinology and Metabolism Volume: 95 Pages: 756-764
  • Peer Reviewed
• [Journal Article] Mutation and Gene Copy Number Analyses of Six Pituitary Transcription Factor Genes in 71 Patients with Combined Pituitary Hormone Deficiency : Identification of a Single Patient with LHX4 Deletion. (2010)
  • Author(s): Dateki S, et al.
  • Journal Title: Journal of Clinical Endocrinology and Metabolism Volume: 95 Pages: 4043-4047
  • Peer Reviewed
• [Journal Article] OTX2遺伝子異常症の臨床的、分子遺伝学的解析 (2010)
  • Author(s): 伊達木澄人, 他
  • Journal Title: ホルモンと臨床 Volume: (In press)
• [Journal Article] Heterozygous OTX2 mutations are associated with variable pituitary phenotype. (2010)
  • Author(s): Dateki S, et al.
  • Journal Title: Journal of Clinical Endocrinology and Metabohsm 95 Pages: 756-764
  • Peer Reviewed
• [Journal Article] OTX2遺伝子異常症の臨床的、分子遺伝学的解析 (2010)
  • Author(s): 伊達木澄人, 他
  • Journal Title: ホルモンと臨床 (In press)
• [Journal Article] An immunologically anomalous but considerably bioactive growth honnoneproduced by a novel GH1 mutation (p.D116E). (2009)
  • Author(s): Dateki S, et al.
  • Journal Title: European Journal of Endocrinology 161 Pages: 301-306
  • Peer Reviewed
• [Presentation] 複合型下垂体機能低下症における包括的変異・ゲノムコピー数解析 (2010)
  • Author(s): 伊達木澄人
  • Organizer: 第44回日本小児内分泌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-10-08
• [Presentation] IGF1R遺伝子領域を含むヘテロ接合性欠失を認めた子宮内発育不全、成長障害の1例 (2010)
  • Author(s): 伊達木澄人, 他
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-26
• [Presentation] 複合型下垂体機能低下症における包括的変異・ゲノムコピー数解析 (2010)
  • Author(s): 伊達木澄人
  • Organizer: 第33回日本小児遺伝学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-22
• [Presentation] OTX2 mutations and hypopituitarism ICE2010 satellite symposia (2010)
  • Author(s): Dateki S.
  • Organizer: Pediatric Endocrinology
  • Place of Presentation: 東京
  • Year and Date: 2010-04-01
• [Presentation] OTX2 mutations and hypopituitarism (2010)
  • Author(s): Dateki S, et al.
  • Organizer: ICE2010 satellite symposia (Pediatric Endocrinology)
  • Place of Presentation: Tokyo
  • Year and Date: 2010-04-01
• [Presentation] Mutation and Gene Copy Number Analyses of Six Pituitary Transcription Factor Genes in 71 Patients with Combined Pituitary Hormone Deficiency : Identification of a Single Patient with LHX4 Deletion. (2010)
  • Author(s): Dateki S.
  • Organizer: 14th International Congress of Endocrinology (ICE2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-28
• [Presentation] 下垂体の発生と疾患、OTX2遺伝子異常症 (2009)
  • Author(s): 伊達木澄人
  • Organizer: Forum on Growth Hormone Research 2009
  • Place of Presentation: 東京
  • Year and Date: 2009-10-17
• [Presentation] OTX2異常症の臨床的、分子遺伝学的解析 (2009)
  • Author(s): 伊達木澄人, 他
  • Organizer: 第43回日本小児内分泌学会学術集会
  • Place of Presentation: 宇都宮
  • Year and Date: 2009-10-02
• [Presentation] OTX2遺伝子異常症の臨床的および分子遺伝学的解析 (2009)
  • Author(s): 伊達木澄人
  • Organizer: 第43回日本小児内分泌学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2009-10-01
• [Presentation] OTX2遺伝子異常症の臨床的,分子遺伝学的解析 (2009)
  • Author(s): 伊達木澄人
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] OTX2異常症の臨床的、分子遺伝学的解析 (2009)
  • Author(s): 伊達木澄人, 他
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] Heterozygous OTX2 mutations are associated with variable pituitary hormone deficiency. (2009)
  • Author(s): Dateki S.
  • Organizer: The 8th Joint meeting, ESPE-LWPES in association with APEG, APPES, SLEP, JSPE.
  • Place of Presentation: New York
  • Year and Date: 2009-09-10
• [Presentation] Heterozygous OTX2 mutations are associated with variable pituitary hormone deficiency (2009)
  • Author(s): Dateki S, et al.
  • Organizer: The 8th Join Meeting ESPE-LWPES
  • Place of Presentation: NEW YORK
  • Year and Date: 2009-09-09
• [Presentation] 無・小眼球症責任遺伝子OTX2は,下垂体発生・機能に関与する (2009)
  • Author(s): 伊達木澄人
  • Organizer: 第82回日本内分泌学会
  • Place of Presentation: 群馬
  • Year and Date: 2009-04-23
• [Presentation] 無・小眼球症責任遺伝子OTX2は下垂体発生・分化に関与する (2009)
  • Author(s): 伊達木澄人
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬
  • Year and Date: 2009-04-22
• [Remarks] ホームページ等
  • URL: http://www.nch.go.jp/endocrinology/kenrin.htm
• [Remarks]
  • URL: http://www.nch.go.jp/endocrinology/kenrin.htm
• [Remarks]
  • URL: http://www.nch.go.jp/endocrinology/kenrin.htm