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Molecular basis of congenital pituitary defect

Research Project

Project/Area Number 20591213
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionHokkaido University

Principal Investigator

TAJIMA Toshihiro  Hokkaido University, 大学院・医学研究科, 講師 (50333597)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords小児内分泌学 / 下垂体 / 発生 / CHD7 / 中枢性性腺機能低 / Septo-optic dysplasai / GLI2 / OTX2 / 複合型下垂体前葉ホルモン欠損 / 中枢性性腺機能低下症 / クロマチンリモデリン / 無眼球症 / 転写因子
Research Abstract

We analyzed 35 patients of congenital pituitary anomalies accompanying with combined pituitary hormone deficiency. As results, we identified novel mutations of the OTX2 gene (p.S136sX178, p.K75fsX103) and one novel mutation (V101A) of the LHX4 gene.
OTX2 is a transcription factor necessary for ocular and forebrain development. This study indicates that the OTX2 gene mutation is a cause of CPHD and the clinical phenotypes of OTX2 mutations involved opthalamogical and central nervous anomalies.
LHX4, a LIM-homeodomain transcription factor, is required for development of the pituitary and nervous system. A novel missense mutation (V101A) was identified. In vitro transfection studies demonstrated that this mutant was loss-of-function. An early report suggested that a poorly developed sella turcica was a characteristic feature caused by a LHX4 mutation. However, our patient had a normally developed sella turcica. Therefore, a poorly developed sella turcica is not a universal feature of patients with LHX4 mutations.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (52 results)

All 2011 2010 2009 2008

All Journal Article (27 results) (of which Peer Reviewed: 22 results) Presentation (25 results)

  • [Journal Article] Congenital hypothyroidism caused by a PAX8 gene mutation manifested as sodium/iodide symporter gene defect.2011

    • Author(s)
      Jo W, Ishizu K, Fujieda K, Tajima T
    • Journal Title

      Journal of Thyroid Research

      Volume: On-line Pages: 12-16

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel PAX4 mutation in a Japanese patient with maturity onset diabetes of the young (MODY)2011

    • Author(s)
      Jo W, Endo M, Nakamura A, Ishidu K, Tajima T.
    • Journal Title

      Tohoku Journal of Experimental Medicine

      Volume: VOL.223 Pages: 113-118

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterozygous orthodenticle homeobox 2 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

      Pages: 756-764

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Loss of function mutation (V101A) in a LIM domain of the LHX4 gene causes combined pituitary hormone deficiency.2010

    • Author(s)
      Tajima T, Ishizu K, Yorifuji T.
    • Journal Title

      Exp Clin Endocrinol Diabetes 118

      Pages: 405-409

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Problems in diagnosing atypical Gitelman's syndrome presenting with normomagnesaemia.2010

    • Author(s)
      Nakamura A, Shimizu C, Nagai S, Yoshida M, Aoki K, Kondo T, Miyoshi H, Wada N, Tajima T, Terauchi Y, Yoshioka N, Koike T
    • Journal Title

      Clin Endocrinol 72

      Pages: 272-276

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased Na reabsorption via the Na-Cl cotransporter in autosomal recessive pseudohypoaldosteronism.2010

    • Author(s)
      Adachi M, Asakura Y, Muroya K, Tajima T, Fujieda K, Kuribayashi E, Uchida S
    • Journal Title

      Clin Exp Nephrol 14

      Pages: 228-232

    • NAID

      10027706204

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of the GATA3 gene in five Japanese patients with HDR syndrome.2010

    • Author(s)
      Nakamura A, Fujiwara F, Hasegawa Y, Ishizu K, Mabe A, Nakagawa H, Nagasaki K, Jo W, Tajima T
    • Journal Title

      Endocr J.[Epub ahead of print]

    • NAID

      10029587711

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 先天性副腎過形成の成因と治療の最近の話題2010

    • Author(s)
      田島敏広、中村明枝、城和歌子、石津桂、奥原宏治、藤枝憲二
    • Journal Title

      日本小児科学会雑誌 114

      Pages: 1373-1380

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 成長ホルモン分泌不全性低身長 小児の薬の使い方2010

    • Author(s)
      田島敏広
    • Journal Title

      小児内科増刊号 42

      Pages: 565-666

    • Related Report
      2010 Final Research Report
  • [Journal Article] Increased Na reabsorption via the Na-Cl cotransporter in autosomal recessive pseudohypoaldosteronism.2010

    • Author(s)
      Adachi M, Asakura Y, Muroya K, Tajima T, Fujieda K, Kuribayashi E, Uchida S.
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: VOL.14 Pages: 228-232

    • NAID

      10027706204

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia.2010

    • Author(s)
      Nanjo K, Nagai S, Shimizu C, Tajima T, Kondo T, Miyoshi H, Yoshioka N, Koike T.
    • Journal Title

      Endocrine Journal

      Volume: VOL.57 Pages: 782-792

    • NAID

      10029586221

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular analysis of the GATA3 gene in five Japanese patients with HDR syndrome.2010

    • Author(s)
      Nakamura A, Fujiwara F, Hasegawa Y, Ishizu K, Mabe A, Nakagawa H, Nagasaki K, Jo W, Tajima T.
    • Journal Title

      Endocrine Journal

      Volume: 58 Pages: 123-130

    • NAID

      10029587711

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype2010

    • Author(s)
      Dateki, et al.
    • Journal Title

      Journal of Endocrinology and Metabolism 95

      Pages: 756-764

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 先天性複合型下垂体機能低下症2009

    • Author(s)
      田島敏広
    • Journal Title

      ゲノム医学 9

      Pages: 55-59

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary.2009

    • Author(s)
      Tajima T, Ohtake A, Hoshino M, Amemiya S, Sasaki N, Ishizu K, Fujieda K
    • Journal Title

      J Clin Endocrinol Metab. 94

      Pages: 314-319

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Results of neonates with elevated free thyroxine levels detected by a neonatal screening system.2009

    • Author(s)
      Tajima T, Jo W, Fujikura K, Fukushi M, Fujieda K
    • Journal Title

      Pediatr Res 66

      Pages: 312-316

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary2009

    • Author(s)
      Tajima T, et al
    • Journal Title

      Journal of Clinical Endocrinology and Metabolism 94

      Pages: 314-319

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Familial hypomagnesemia with hypercalciuria and nephrocalcinosis : unusual clinical associations and novel claudin16 mutation in an Egyptian family2009

    • Author(s)
      Al-Haggar M, et al.
    • Journal Title

      Clinical and Experimental Nephrology 13

      Pages: 288-294

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel heterozygous mutation of steroidogenic factor-1(SF-1/Ad4BP)gene(NR5A1)in a 46, XY disorders of sex development(DSD)patient without adrenal failure.2009

    • Author(s)
      Tajima T, et al.
    • Journal Title

      Endocrine Journal 56

      Pages: 619-624

    • NAID

      10026914347

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Mutation(V101A) of the LHX4 Gene in a Japanese Patient with Combined Pituitary Hormone Deficiency.2009

    • Author(s)
      Tajima T, et al.
    • Journal Title

      Experimental and Clinical Endocrinology and Met abolism (e-pub)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elevated free thyroxine levels detected by a neonatal screening system.2009

    • Author(s)
      Tajima T, et al.
    • Journal Title

      Pediatric Research 66

      Pages: 312-316

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      田島敏広
    • Journal Title

      小児内分泌学(診断と治療社)

      Pages: 178-183

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 複合型下垂体機能不全 小児疾患診療のための病態生理2008

    • Author(s)
      田島敏広
    • Journal Title

      小児内科 40

      Pages: 661-666

    • Related Report
      2010 Final Research Report
  • [Journal Article] Prenatal diagnosis and treatment of steroid 21-hydroxylase deficiency.2008

    • Author(s)
      田島敏広, 藤枝憲二
    • Journal Title

      Clin Pediatr Endocrinol. 17

      Pages: 95-102

    • NAID

      10031199581

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Case study of a 15-year-old boy with McCune-Albright syndrome combined with pituitary gigantism : effect of octreotide-long acting release (LAR) and cabergoline therapy.2008

    • Author(s)
      Tajima T, Tsubaki J, Ishizu K, Jo W, Ishi N, Fujieda K
    • Journal Title

      Endocr J. 55

      Pages: 595-599

    • NAID

      10021266702

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Four Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism caused by DAX-1 gene mutations : mutant DAX-1 failed to repress steroidogenic acute regulatory protein (StAR) and luteinizing hormone beta-subunit gene promoter activity.2008

    • Author(s)
      Okuhara K, Abe S, Kondo T, Fujita K, Koda N, Mochizuki H, Fujieda K, Tajima T
    • Journal Title

      Endocr J. 55

      Pages: 97-103

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 複合型下垂体機能不全小児疾患診療のための病態生理2008

    • Author(s)
      田島敏広
    • Journal Title

      小児内科 40

      Pages: 661-666

    • Related Report
      2008 Annual Research Report
  • [Presentation] 思春期発来異常へのアプローチ2011

    • Author(s)
      田島敏広
    • Organizer
      第20回臨床内分泌up date
    • Place of Presentation
      札幌
    • Year and Date
      2011-01-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 思春期発来異常へのアプローチ2011

    • Author(s)
      田島敏広
    • Organizer
      第20回臨床内分泌Up date
    • Place of Presentation
      札幌コンベンションセンター(北海道) 招待講演
    • Year and Date
      2011-01-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] TSH受容体機能獲得型異常による甲状腺機能亢進症の1家系2011

    • Author(s)
      中村明枝、青柳隼人、石津桂、田島敏広
    • Organizer
      第20回臨床内分泌Up date
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2011-01-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 治療に難渋しアイソトープ治療をおこなった小児バセドウ病の3例2011

    • Author(s)
      石津桂、竹井俊樹、中村明枝、田島敏広
    • Organizer
      第20回臨床内分泌Up date
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2011-01-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 当院で経験したSepto-Optic Dysplasiaの2症例2011

    • Author(s)
      高梨久仁子, 高田晋, 越田慎一, 杉山未奈子, 野呂歩, 鈴木靖人, 仲西正憲, 永島哲郎, 田島敏広
    • Organizer
      第20回小児内分泌研究会
    • Place of Presentation
      札幌京王プラザホテル(北海道)
    • Year and Date
      2011-01-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] CHRGE症候群の4例2010

    • Author(s)
      中村明枝、石津桂、田島敏広
    • Organizer
      第44回日本小児内分泌学会学術集会
    • Place of Presentation
      大阪市中央会議堂(大阪府)
    • Year and Date
      2010-10-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Congenital hypothyroidism caused by a PAX8 gene mutation manifested as sodium/iodide symporter gene defect.2010

    • Author(s)
      Jo W、Endo M, Ishizu K, Nakamura A, Tajima T
    • Organizer
      49^<th> Annual Meeting of the European Society for Pediatric Endocrinology
    • Place of Presentation
      プラハコンベンションセンター(チェコ)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Dr Kenji Fujieda Memorial Lecture2010

    • Author(s)
      田島敏広
    • Organizer
      49^<th> Annual Meeting of the European Society for Pediatric Endocrinology
    • Place of Presentation
      プラハ
    • Year and Date
      2010-09-24
    • Related Report
      2010 Final Research Report
  • [Presentation] Dr Kenji Fujieda Memorial Lecture2010

    • Author(s)
      Tajima T
    • Organizer
      49^<th> Annual Meeting of the European Society for Pediatric Endocrinology
    • Place of Presentation
      プラハコンベンションセンター(チェコ) 招待講演
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Longitudinal growth of patients with 21-hydroxylase deficiency.2010

    • Author(s)
      Nakamura A, Jo W, Ishizu K, Tajima T, Fujieda K
    • Organizer
      International Symposium on Pediatric Endocrinology
    • Place of Presentation
      東京
    • Year and Date
      2010-03-31
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular basis and clinical phenotypes caused by OTX2 gene defects in combined pituitary hormone deficiency.2010

    • Author(s)
      Tajima T, Nakamura A, Ishizu K, Jo W
    • Organizer
      14th International Congress of Endocrinology.
    • Place of Presentation
      京都
    • Year and Date
      2010-03-29
    • Related Report
      2010 Final Research Report
  • [Presentation] Cytochrome P450scc as a cause of congenital adrenal hyperplasia (lipoid CAH)2010

    • Author(s)
      田島敏広, 藤枝憲二
    • Place of Presentation
      京都
    • Year and Date
      2010-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 思春期発来異常をめくる諸問題2009

    • Author(s)
      田島敏広
    • 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
      2009-10-03
    • Related Report
      2010 Final Research Report
  • [Presentation] 思春期発来異常をめぐる諸問題2009

    • Author(s)
      田島敏広
    • Organizer
      第43回日本小児内分泌学会学術集会
    • Place of Presentation
      宇都宮、栃木県総合文化センター
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical and molecular genetic spectrum of lipoid CAH and noncalssic lipoid CAH.2009

    • Author(s)
      田島敏広, 藤枝憲二
    • Organizer
      LWPES/ESPE 8^<th> Joint Meeting Global Care in Pediatric Endocrinology
    • Place of Presentation
      ニューヨーク
    • Year and Date
      2009-09-13
    • Related Report
      2010 Final Research Report
  • [Presentation] Clinical and molecular genetic spectrum of lipoid CAH and nonclassic lipoid CAH2009

    • Author(s)
      Tajima T, et al.
    • Organizer
      LWPES/ESPE 8^<th> Joint Meeting Global Care in Pediatric Endocrinology
    • Place of Presentation
      New York, Hilton hotel USA
    • Year and Date
      2009-09-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新生児スクリーニングで見つかる先天性副腎過形成症-健やかな成長を目指して-2009

    • Author(s)
      田島敏広
    • Organizer
      第36回日本マススクリーニング学会
    • Place of Presentation
      札幌
    • Year and Date
      2009-08-21
    • Related Report
      2010 Final Research Report
  • [Presentation] 新生児スクリーニングでみつかる先天性副腎過形-すこやかな成長を目指して-2009

    • Author(s)
      田島敏広
    • Organizer
      第36回日本マススクリーニング学会
    • Place of Presentation
      札幌、札幌エルプラザ
    • Year and Date
      2009-08-21
    • Related Report
      2009 Annual Research Report
  • [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, 他
    • Organizer
      第82回日本内分泌学会学術集会
    • Place of Presentation
      前橋、群馬県民会館
    • Year and Date
      2009-04-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 下垂体柄欠損を伴った先天性視床下部下垂体機能低症の1例2009

    • Author(s)
      池袋香織, 他
    • Organizer
      第82回日本内分泌学会学術集会
    • Place of Presentation
      前橋、群馬県民会館
    • Year and Date
      2009-04-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 先天性副腎過形成症のトランジッションについて2009

    • Author(s)
      田島敏広、藤枝憲二
    • Organizer
      第19回臨床内分泌代謝up date
    • Place of Presentation
      東京
    • Year and Date
      2009-03-14
    • Related Report
      2010 Final Research Report
  • [Presentation] 先天性下垂体疾患における新たな転写因子異常の展開2008

    • Author(s)
      田島敏広, 他
    • Organizer
      第42回日本小児内分泌学会学術集会
    • Place of Presentation
      米子コンベンションセンター
    • Year and Date
      2008-10-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] Two novel mutations of the oTX2 causes anophthalmia, pituitary ectopic posterior lobe and combined pituitary hormone deficiency.2008

    • Author(s)
      Tajima T, Ishidu K, Otake A, Amamiya S, Kosaka K, Hoshino M
    • Organizer
      90^<th> annual meeting of Endocrine Society.
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2008-06-17
    • Related Report
      2010 Final Research Report
  • [Presentation] 下垂体形成異常におけるOTX2の役割2008

    • Author(s)
      田島敏広、石津桂、星野正也、大竹明、雨宮伸、佐々木望、藤枝憲二
    • Organizer
      第81回日本内分泌学会学術総会
    • Place of Presentation
      青森
    • Year and Date
      2008-05-17
    • Related Report
      2010 Final Research Report
  • [Presentation] 下垂体形成異常におけるOTX2の役割2008

    • Author(s)
      田島敏広, 他
    • Organizer
      第81回日本内分泌学会学術総会
    • Place of Presentation
      ホテル青森
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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