Analysis of a novel factor associated with short stature and application to therapy

• Project/Area Number: 26670494
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: Kitanaka Sachiko 東京大学, 医学部附属病院, 准教授 (30431638)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 低身長 / モデル動物 / 発症機序

Outline of Final Research Achievements

Short stature is one of the most common symptoms in pediatric endocrine diseases. We recently found a novel factor responsible for a disease presenting with extreme short stature. In this study, we analyzed the mechanism of this factor related to bone growth. We overexpressed this factor in a cultured cell line and evaluated the cell growth, cell differentiation, and marker proteins. We found that this factor had a repressive effect on chondrocyte growth and differentiation. The repressive effect was increased in the mutants. Furthermore, we have created model animals to investigate the function of this factor in vivo.

Research Products

• [Journal Article] Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy. (2017)
  • Author(s): Harita Y, Kitanaka S, Isojima T, Ashida A, Hattori M
  • Journal Title: Pediatr Nephrol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Partial monosomy of 10p and duplication of another chromosome in two patients. (2017)
  • Author(s): Ohta S, Isojima T, Mizuno Y, Kato M, Mimaki M, Seki M, Sato Y, Ogawa S, Takita J, Kitanaka S, Oka A.
  • Journal Title: Pediatr Int. Volume: 59 Issue: 1 Pages: 99-102
  • DOI: 10.1111/ped.13181
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] nail-patella症候群（爪膝蓋骨症候群） (2016)
  • Author(s): 北中幸子、張田豊
  • Journal Title: 小児科診療 Volume: 79増 Pages: 309-309
• [Journal Article] カルシウムを多く摂取すると身長が伸びる？ (2016)
  • Author(s): 北中幸子
  • Journal Title: 小児内科 Volume: 48 Pages: 918-919
• [Journal Article] ビタミンD依存性くる病／骨軟化症 (2016)
  • Author(s): 北中幸子
  • Journal Title: 最新医学 Volume: 72 Pages: 1943-1948
• [Journal Article] ビタミンD依存症の病因と治療 (2016)
  • Author(s): 北中幸子
  • Journal Title: Clinical Calcium Volume: 26 Pages: 277-283
• [Journal Article] Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: A novel mechanism of dominant inheritance. (2015)
  • Author(s): Isojima T, Ishizawa M, Yoshimura K, Tamura M, Hirose S, Makishima M, Kitanaka S.
  • Journal Title: Bone Reports Volume: 2 Pages: 68-73
  • DOI: 10.1016/j.bonr.2015.05.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detection of hereditary 1,25-hydroxyvitamin D-resistant rickets caused by uniparental disomy of chromosome 12 using genome-wide single nucleotide polymorphism array. (2015)
  • Author(s): Tamura M, Isojima T, Kawashima M, Yoshida H, Yamamoto K, Kitaoka T, Namba N, Oka A, Ozono K, Tokunaga K, Kitanaka S
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0131157-e0131157
  • DOI: 10.1371/journal.pone.0131157
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mineral status of premature infants in early life and linear growth at age three. (2015)
  • Author(s): Isojima T, Kushima R, Goishi K, Tsuchida S, Watanabe T, Takahashi N, Kitanaka S
  • Journal Title: Pediatr Int Volume: 57 Issue: 5 Pages: 864-9
  • DOI: 10.1111/ped.12657
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Successful intermittent intravenous calcium treatment via the peripheral route in a patient with hereditary vitamin D-resistant rickets and alopecia. (2015)
  • Author(s): Ersoy B, Kiremitci S, Isojima T, Kitanaka S
  • Journal Title: Horm Res Paediatr. Volume: 83 Issue: 1 Pages: 67-72
  • DOI: 10.1159/000367711
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Kenny Caffey症候群と類縁疾患 (2015)
  • Author(s): 磯島豪、北中幸子
  • Journal Title: 日本臨床 Volume: 73 Pages: 1959-1964
• [Journal Article] LMX1B Mutation with Residual Transcriptional Activity as a Cause of Isolated Glomerulopathy. (2014)
  • Author(s): Isojima T, Harita Y, Furuyama M, Sugawara N, Ishizuka K, Horita S, Kajiho Y, Miura K, Igarashi T, Hattori M, Kitanaka S
  • Journal Title: Nephrol Dial Transplant Volume: 29 Issue: 1 Pages: 81-8
  • DOI: 10.1093/ndt/gft359
  • Peer Reviewed
• [Journal Article] A recurrent de novo FAM111A mutation causes Kenny–Caffey syndrome type 2. (2013)
  • Author(s): Isojima T, Doi K, Mitsui J, Oda Y, Tokuhiro E, Yasoda A, Yorifuji T, Horikawa R, Yoshimura J, Ishiura H, Morishita S, Tsuji S, and Kitanaka S.
  • Journal Title: J Bone Mineral Res Volume: 29 Issue: 4 Pages: 992-998
  • DOI: 10.1002/jbmr.2091
  • Peer Reviewed / Open Access
• [Presentation] Analysis of COL10A1 gene is useful to detect metaphyseal chondrodysplasia Schmid type for the differential diagnosis of bow-legs. (2016)
  • Author(s): Hiroyuki Tanaka, Mayuko Tamura, Chie Takahashi, Tsuyoshi Isojima, Nobuhiko Haga, Akira Oka, Sachiko Kitanaka.
  • Organizer: The 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society
  • Place of Presentation: 国際フォーラム（東京都中央区）
  • Year and Date: 2016-11-17
• [Presentation] A case with duplication of 20qter and deletion of 20pter due to maternal pericentric inversion, presenting with Silver-Russell syndrome-like phenotypes. (2016)
  • Author(s): Chie Takahashi, Akie Nakamura, Mayuko Tamura, Hiroyuki Tanaka, Tsuyoshi Isojima, Akira Oka, Masayo Kagami, Sachiko Kitanaka.
  • Organizer: The 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society
  • Place of Presentation: 国際フォーラム（東京都中央区）
  • Year and Date: 2016-11-17
• [Presentation] rFSH monotherapy prior to hCG-rFSH combination therapy is an effective new treatment to achieving future fertility in adolescent patients with congenital male hypogonadotropic hypogonadism. (2016)
  • Author(s): Sato N, Hosokawa A, Kitanaka S, Yoshizawa A, Noda M, Tanaka T
  • Organizer: The 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society
  • Place of Presentation: 国際フォーラム（東京都中央区）
  • Year and Date: 2016-11-17
• [Presentation] レセプトデータによる小児ビタミンD欠乏性くる病有病率の10年間の推移 (2016)
  • Author(s): 伊藤明子、冨尾淳、田村麻由子、磯島豪、小林廉毅、北中幸子
  • Organizer: 第89回日本内分泌学会
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2016-04-21
• [Presentation] 禿頭をきたすビタミンD受容体遺伝子の新規変異の機能解析 (2015)
  • Author(s): 田村麻由子、石澤通康、磯島豪、岡明、槇島誠、北中幸子
  • Organizer: 第49回日本小児内分泌学会学術集会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-10-08
• [Presentation] くる病・ビタミンD欠乏症90例における遺伝子診断をもとにした病型別臨床所見 (2015)
  • Author(s): 北中幸子、田村麻由子、磯島豪
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ニューオータニ（東京都港区）
  • Year and Date: 2015-04-23
• [Presentation] ビタミンD依存性くる病2型の7家系におけるビタミンD受容体遺伝子の3種類の新規変異とその機能解析 (2015)
  • Author(s): 田村麻由子、磯島豪、北中幸子
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ニューオータニ（東京都港区）
  • Year and Date: 2015-04-23
• [Presentation] 性分化疾患から早期診断しコレステロール治療を行ったSmith-Lemli-Opitz症候群の１例 (2015)
  • Author(s): 152.田村 麻由子、真船 亮、安戸 裕貴、下田 木の実、磯島 豪、笠間 健嗣、高橋 尚人、北中 幸子、岡 明
  • Organizer: 第118回日本小児科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-17
• [Presentation] Y染色体長腕欠失とKabuki症候群 (2014)
  • Author(s): 北中幸子、田村麻由子、磯島豪、石井礼花、岡明、三宅紀子、松本直通、永井敏郎
  • Organizer: 第59回日本人類遺伝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] くる病・ビタミンD欠乏症88例の臨床的検討 (2014)
  • Author(s): 北中幸子、田村麻由子、磯島豪
  • Organizer: 第48回日本小児内分泌学会学術集会
  • Place of Presentation: 静岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ビタミンD受容体遺伝子解析で3種類の新規変異を認めたビタミンD依存性くる病2型の7家系 (2014)
  • Author(s): 田村麻由子、磯島豪、北中幸子
  • Organizer: 第48回日本小児内分泌学会学術集会
  • Place of Presentation: 静岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 染色体Gバンド分析で見いだせなかった不均衡転座をSNPアレイにより同定した10p-症候群の1例 (2014)
  • Author(s): 磯島豪、田村麻由子、太田さやか、加藤元博、三牧正和、滝田順子、北中幸子、岡明
  • Organizer: 第48回日本小児内分泌学会学術集会
  • Place of Presentation: 静岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Book] 小児疾患ガイドライン－最新の診療指針第3版 (2016)
  • Author(s): 北中幸子
  • Total Pages: 670
  • Publisher: 総合医学社
• [Book] 難病事典 (2015)
  • Author(s): 北中幸子
  • Total Pages: 511
  • Publisher: 学研メディカル秀潤社
• [Book] 今日の治療指針2014 (2014)
  • Author(s): 北中幸子
  • Total Pages: 1900
  • Publisher: 医学書院
• [Book] 小児科研修医ノート (2014)
  • Author(s): 北中幸子
  • Total Pages: 539
  • Publisher: 診断と治療社