• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Investigation of genetic etiology of rare diseases with craniofacial deformities

Research Project

Project/Area Number 19H03858
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionOsaka University

Principal Investigator

Kurosaka Hiroshi  大阪大学, 歯学部附属病院, 講師 (20509369)

Co-Investigator(Kenkyū-buntansha) 犬伏 俊博  大阪大学, 歯学研究科, 講師 (30550941)
中谷 明弘  東京大学, 大学院新領域創成科学研究科, 特任教授 (60301149)
山城 隆  大阪大学, 歯学研究科, 教授 (70294428)
真下 知士  東京大学, 医科学研究所, 教授 (80397554)
沖 真弥  京都大学, 医学研究科, 特定准教授 (90452713)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords顎顔面形成不全 / 希少疾患 / 動物モデル / ゲノム解析 / レチノイン酸シグナル / Gata3 / 口唇口蓋裂 / ゲノム / 遺伝子変異 / 疾患モデル
Outline of Research at the Start

顎顔面の形成は様々な顔面突起が成長や癒合を繰り返し精巧に行う事により達成される。これらの顔面突起の成長や癒合が阻害されると口唇口蓋裂等を始めとする多様な顎顔面形成不全症状が誘発される。全ての遺伝的先天性疾患の中でも顎顔面形成不全症状を示す物は非常に多い。本研究では患者本人及び家族のエクソームや全ゲノム解析を行い健常者との比較を行うことで、より効率的に顎顔面形成不全症状と関連する遺伝子変異を同定し、疾患の特徴等と照らし合わせて同変異の果たす生物学的役割や他の遺伝子との関連性などを探索する事を目的とする。

Outline of Final Research Achievements

Congenital craniofacial defects are one of the most frequent symptoms which could be detected among all congenital diseases. In the present research project, we investigated the genetic cause of undiagnosed diseases with broad craniofacial anomalies. Among the patients who are enrolled in this project, we identified 5 genetic loci which are associated with individual diseases and succeeded to make precise diagnoses such as Baraitser-Winter syndrome and Pseudohypoparathyroidism. We also established some cellular and animal models for these identified diseases in order to further investigate the molecular and cellular mechanisms for rare craniofacial disorders.

Academic Significance and Societal Importance of the Research Achievements

現在、口唇口蓋裂等の顎顔面形成不全を伴う稀少疾患の多くは根本的な治療法が存在せず、それ以前に原因も解らない場合がほとんどである。また今までも多くの研究がこの様な未診断疾患の遺伝的原因の究明を試みているが全ての症例で原因遺伝子が同定されている訳ではない。本研究課題を推進する事により顎顔面領域を含んだ多臓器にわたる稀少疾患の遺伝的要因の解明が可能であり、その様な多様な症状を引き起こす分子基盤を解明する事が出来た。原因が解明されれば治療法の開発に繋がり社会的な意義が大きい。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (44 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (19 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 19 results,  Open Access: 9 results) Presentation (22 results) (of which Int'l Joint Research: 6 results,  Invited: 9 results)

  • [Int'l Joint Research] Stowers Institute for Medical Research/University of Louisville(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Stowers Institute for Medical Research/University of Lousville(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Stowers Institute for Medical Research(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis2022

    • Author(s)
      Inubushi Toshihiro、Fujiwara Ayaka、Hirose Takumi、Aoyama Gozo、Uchihashi Toshihiro、Yoshida Naoki、Shiraishi Yuki、Usami Yu、Kurosaka Hiroshi、Toyosawa Satoru、Tanaka Susumu、Watabe Tetsuro、Kogo Mikihiko、Yamashiro Takashi
    • Journal Title

      Disease Models & Mechanisms

      Volume: 15 Issue: 2

    • DOI

      10.1242/dmm.049093

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects2022

    • Author(s)
      Wu Y.、Kurosaka H.、Wang Q.、Inubushi T.、Nakatsugawa K.、Kikuchi M.、Ohara H.、Tsujimoto T.、Natsuyama S.、Shida Y.、Sandell L.L.、Trainor P.A.、Yamashiro T.
    • Journal Title

      Journal of Dental Research

      Volume: In press Issue: 6 Pages: 686-694

    • DOI

      10.1177/00220345211062049

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of dentition: From initiation to occlusion and related diseases2022

    • Author(s)
      Kurosaka Hiroshi、Itoh Shinsuke、Morita Chisato、Tsujimoto Takayuki、Murata Yuka、Inubushi Toshihiro、Yamashiro Takashi
    • Journal Title

      Journal of Oral Biosciences

      Volume: In press Issue: 2 Pages: 159-164

    • DOI

      10.1016/j.job.2022.02.005

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling2021

    • Author(s)
      Wang Qi、Xu Lin、Miura Jiro、Saha Mithun Kumar、Uemura Yume、Sandell Lisa L.、Trainor Paul A.、Yamashiro Takashi、Kurosaka Hiroshi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 596838-596838

    • DOI

      10.3389/fcell.2021.596838

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracellular and Intercellular Gene Regulatory Network Inference From Time-Course Individual RNA-Seq2021

    • Author(s)
      Kashima Makoto、Shida Yuki、Yamashiro Takashi、Hirata Hiromi、Kurosaka Hiroshi
    • Journal Title

      Frontiers in Bioinformatics

      Volume: 1

    • DOI

      10.3389/fbinf.2021.777299

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation2021

    • Author(s)
      Kurosaka Hiroshi、Mushiake Jin、Saha Mithun、Wu Yanran、Wang Qi、Kikuchi Masataka、Nakaya Akihiro、Yamamoto Sayuri、Inubushi Toshihiro、Koga Satoshi、Sandell Lisa L、Trainor Paul A、Yamashiro Takashi
    • Journal Title

      Human Molecular Genetics

      Volume: 30 Issue: 24 Pages: 2383-2392

    • DOI

      10.1093/hmg/ddab205

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice2021

    • Author(s)
      Nakamura Eriko、Hata Kenji、Takahata Yoshifumi、Kurosaka Hiroshi、Abe Makoto、Abe Takaya、Kihara Miho、Komori Toshihisa、Kobayashi Sachi、Murakami Tomohiko、Inubushi Toshihiro、Yamashiro Takashi、Yamamoto Shiori、Akiyama Haruhiko、Kawaguchi Makoto、Sakata Nobuo、Nishimura Riko
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1258-1258

    • DOI

      10.1038/s42003-021-02793-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Association Between Runx Signaling and Craniofacial Development and Disease2021

    • Author(s)
      Yamashiro Takashi、Kurosaka Hiroshi、Inubushi Toshihiro
    • Journal Title

      Current Osteoporosis Reports

      Volume: 20 Issue: 1 Pages: 120-126

    • DOI

      10.1007/s11914-021-00692-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fork‐shaped mandibular incisors as a novel phenotype of LRP5 ‐associated disorder2021

    • Author(s)
      Yamada Mamiko、Kubota Kazumi、Uchida Atsuro、Yagihashi Tatsuhiko、Kawasaki Masahito、Suzuki Hisato、Uehara Tomoko、Takenouchi Toshiki、Kurosaka Hiroshi、Kosaki Kenjiro
    • Journal Title

      American Journal of Medical Genetics Part A

      Volume: 185 Issue: 5 Pages: 1544-1549

    • DOI

      10.1002/ajmg.a.62132

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive Orthodontic Treatment of a Patient With Prader?Willi Syndrome2020

    • Author(s)
      Uemura Yume、Oka Ayaka、Kurosaka Hiroshi、Yamashiro Takashi
    • Journal Title

      The Cleft Palate-Craniofacial Journal

      Volume: online ahead of print Issue: 11 Pages: 1459-1467

    • DOI

      10.1177/1055665620977375

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Observation of the Epithelial Cell Behavior in the Nasal Septum During Primary Palate Closure in Mice2020

    • Author(s)
      Yamamoto Sayuri、Kurosaka Hiroshi、Miura Jiro、Aoyama Gozo、Sarper Safiye Esra、Oka Ayaka、Inubushi Toshihiro、Nakatsugawa Kohei、Usami Yu、Toyosawa Satoru、Yamashiro Takashi
    • Journal Title

      Frontiers in Physiology

      Volume: 11 Pages: 1-1

    • DOI

      10.3389/fphys.2020.538835

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Orthognathic treatment of patient with missing permanent first molars2020

    • Author(s)
      Nakatsugawa Kohei、Kurosaka Hiroshi、Yamashiro Takashi
    • Journal Title

      Orthodontic Waves

      Volume: 79 Issue: 2-3 Pages: 135-143

    • DOI

      10.1080/13440241.2020.1822062

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Surgical and orthodontic approach for a patient with a severely constricted maxillary arch caused by bilateral cleft lip and palate2020

    • Author(s)
      Oka Ayaka、Kurosaka Hiroshi、Nakatsugawa Kohei、Yamashiro Takashi
    • Journal Title

      Orthodontic Waves

      Volume: 79 Issue: 2-3 Pages: 127-134

    • DOI

      10.1080/13440241.2020.1751456

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multidisciplinary Approach for Treating Malocclusion of Patient With Basal Cell Nevus Syndrome: A Case Report2019

    • Author(s)
      Inoue Sayuri、Kurosaka Hiroshi、Lee Donghoon、Yamashiro Takashi
    • Journal Title

      The Cleft Palate-Craniofacial Journal

      Volume: 57 Issue: 2 Pages: 255-262

    • DOI

      10.1177/1055665619866562

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anterior cleft palate due to Cbfb deficiency and its rescue by folic acid2019

    • Author(s)
      Sarper Safiye E.、Inubushi Toshihiro、Kurosaka Hiroshi、Ono Minagi Hitomi、Murata Yuka、Kuremoto Koh-ichi、Sakai Takayoshi、Taniuchi Ichiro、Yamashiro Takashi
    • Journal Title

      Disease Models & Mechanisms

      Volume: 12 Issue: 6 Pages: 038851-038851

    • DOI

      10.1242/dmm.038851

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Perturbed development of cranial neural crest cells in association with reduced sonic hedgehog signaling underlies the pathogenesis of retinoic-acid-induced cleft palate2019

    • Author(s)
      Wang Qi、Kurosaka Hiroshi、Kikuchi Masataka、Nakaya Akihiro、Trainor Paul A.、Yamashiro Takashi
    • Journal Title

      Disease Models & Mechanisms

      Volume: 12 Issue: 10 Pages: 040279-040279

    • DOI

      10.1242/dmm.040279

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Observation of Dynamic Cellular Migration of the Medial Edge Epithelium of the Palatal Shelf in vitro2019

    • Author(s)
      Aoyama Gozo、Kurosaka Hiroshi、Oka Ayaka、Nakatsugawa Kohei、Yamamoto Sayuri、Sarper Safiye Esra、Usami Yu、Toyosawa Satoru、Inubushi Toshihiro、Isogai Yukako、Yamashiro Takashi
    • Journal Title

      Frontiers in Physiology

      Volume: 10

    • DOI

      10.3389/fphys.2019.00698

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stage- and tissue-specific effect of cyclophosphamide during tooth development2019

    • Author(s)
      Nakatsugawa Kohei、Kurosaka Hiroshi、Inubushi Toshihiro、Aoyama Gozo、Isogai Yukako、Usami Yu、Toyosawa Satoru、Yamashiro Takashi
    • Journal Title

      European Journal of Orthodontics

      Volume: - Issue: 5 Pages: 519-530

    • DOI

      10.1093/ejo/cjz002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of craniofacial character of glucose transporter type 1 deficiency syndrome2019

    • Author(s)
      Itoh S, Kurosaka H, Murata Y, Morita C, Kagitani-Shimono K, Nabatame S, Ozono K, Yamashiro T.
    • Journal Title

      Orthodont Waves

      Volume: 78 Issue: 4 Pages: 151-159

    • DOI

      10.1016/j.odw.2019.10.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 希少遺伝性疾患治療における矯正歯科の役割2022

    • Author(s)
      黒坂 寛
    • Organizer
      第2回 せとうち臨床遺伝研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 顎顔面形成不全を伴う希少疾患における矯正歯科治療の役割2021

    • Author(s)
      黒坂 寛
    • Organizer
      第80回日本矯正歯科学会学術大会&第5回国際会議
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Investigating the etiology of rare genetic craniofacial anomalies2021

    • Author(s)
      黒坂 寛
    • Organizer
      INNO-Dent Convergence Bioscience II, Yonsei University
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of orthodontist in the treatment of cases with rare genetic diseases2021

    • Author(s)
      黒坂 寛
    • Organizer
      Orthodontic Joint Seminar between Osaka University and University of Illinois Chicago
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Roles of Orthodontics in The Treatment of Rare Diseases with Craniofacial Deformities2021

    • Author(s)
      黒坂 寛
    • Organizer
      1st International Turkish Japanese Dentistry Congress, 2nd Ankara-Osaka University Dental Workshop
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 頭蓋顎顔面形成における新規ヒアルロン酸分解酵素Tmem2の役割2021

    • Author(s)
      ナグ ビリヤンカ、犬伏 俊博、中西 祐一郎、黒坂 寛、山口 祐、山城 隆
    • Organizer
      第45回日本口蓋裂学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 小児腫瘍治療経験者における顎顔面形態と永久歯の形成状態の特徴2021

    • Author(s)
      中津川 昂平、黒坂 寛、山城 隆
    • Organizer
      第63回近畿東海矯正歯科学会学術大会・総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Baraitser-Winter syndrome を引き起こすACTBの新規変異同定と機能解析2021

    • Author(s)
      辻本 貴行、黒坂 寛、村田 有香、犬伏 俊博、森田 知里、山城 隆
    • Organizer
      第61回日本先天異常学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 顎顔面形成におけるGATA3の組織特異的役割2021

    • Author(s)
      サハ ミスン、黒坂 寛、虫明 仁、犬伏 俊博、山城 隆
    • Organizer
      第61回日本先天異常学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 遺伝子パネル検査を用いた顎顔面領域における先天異常の原因遺伝子探索2021

    • Author(s)
      伊藤 慎将、黒坂 寛、森田 知里、辻本 貴行、村田 有香、犬伏 俊博、山城 隆
    • Organizer
      第61回日本先天異常学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] グルコーストランスポーターI欠損症を伴う不正咬合の外科的矯正治療2021

    • Author(s)
      中西 祐一郎、黒坂 寛、三原 聖美、犬伏 俊博、山城 隆
    • Organizer
      第80回日本矯正歯科学会学術大会&第5回国際会議
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口蓋突起癒合におけるデキサメタゾン(DEX)投与の影響について2021

    • Author(s)
      廣瀬 匠、犬伏 俊博、吉田 尚起、黒坂 寛、青山 剛三、山城 隆
    • Organizer
      第80回日本矯正歯科学会学術大会&第5回国際会議
    • Related Report
      2021 Annual Research Report
  • [Presentation] Baraitser-Winter syndromeを引き起こすACTBの新規変異同定と機能解析2021

    • Author(s)
      辻本 貴行、黒坂 寛、村田 有香、犬伏 俊博、森田 知里、山城 隆
    • Organizer
      第80回日本矯正歯科学会学術大会&第5回国際会議
    • Related Report
      2021 Annual Research Report
  • [Presentation] 顎顔面形成不全を伴う希少疾患研究の病態解明から診断法治療開発法への展開2020

    • Author(s)
      黒坂 寛
    • Organizer
      第62回 歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] レチノイン酸シグナルと顔面形成不全2020

    • Author(s)
      黒坂 寛
    • Organizer
      第60回 日本先天異常学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 顎顔面発生におけるGATA-3の役割2019

    • Author(s)
      サハ・クマル, 黒坂 寛, 山城 隆
    • Organizer
      日本口蓋裂学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 両側性唇顎口蓋裂を伴うCHARGE症候群の一症例2019

    • Author(s)
      白石優季, 黒坂寛, 山城隆
    • Organizer
      日本口蓋裂学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規遺伝子抑制法を用いた口蓋形成の制御機構解明への新たな取り組み2019

    • Author(s)
      犬伏 俊博, 廣瀬 匠, 吉田 尚起, 黒坂 寛, 杉山 弘, 山城 隆
    • Organizer
      歯科基礎医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス二次口蓋における口蓋突起癒合時のmedial edge epithelial cellの動態2019

    • Author(s)
      青山 剛三, 黒坂 寛, 岡 綾香, 中津川 昂平, 山本 沙優里, 宇佐美 悠, 豊澤 悟, 犬伏 俊博, 磯貝 由佳子, 山城 隆
    • Organizer
      日本矯正歯科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 小児がん治療が顎顔面形態と永久歯歯胚形成に与える影響2019

    • Author(s)
      中津川 昂平, 黒坂 寛, 山城 隆
    • Organizer
      日本矯正歯科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The role of retinoic acid signaling for developing the face2019

    • Author(s)
      黒坂 寛
    • Organizer
      The 59th Annual Meeting of The Japanese Teratology Society The 13th World Congress of The International Cleft Lip and Palate Foundation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synergistic Role of GATA3 and Retinoic Acid Signaling in Primitive Choanae Development2019

    • Author(s)
      黒坂 寛
    • Organizer
      Gordon Research Conference Craniofacial Morphogenesis and Tissue Regeneration
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi