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The comprehesive analysis of human hereditary deafness

Research Project

Project/Area Number 17H04345
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionShinshu University

Principal Investigator

Kitajiri Shin-ichiro  信州大学, 学術研究院医学系(医学部附属病院), 講師 (00532970)

Co-Investigator(Kenkyū-buntansha) 宇佐美 真一  信州大学, 学術研究院医学系, 教授 (10184996)
喜多 知子 (嶋知子)  京都大学, 医学研究科, 研究員 (20362519)
西尾 信哉  信州大学, 医学部, 特任講師 (70467166)
大西 弘恵  京都大学, 医学研究科, 研究員 (50397634)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsDIAPH1 / CLDN14 / OTOA / MYO6 / POLD1 / EPHA2 / 遺伝性難聴 / 聴覚 / 内耳機能 / TRIOBP / リポジトリ / 新規変異 / 機能解析 / 内耳 / 難聴 / 遺伝子 / MYPT / 耳科学 / 細胞生物学 / 遺伝学
Outline of Final Research Achievements

In this study, we collected and analyzed genome samples from human deafness pedigrees. The mutation of DID domain of DIAPH1 cause loss of autoinhibition leading to deafness. We identified the first CLDN14 mutation in east Asian population, and the cochlear implantation improved the hearing. The copy number variation of OTOA was significant cause of hearing loss. The myosin VI mutants inhibit the elongation of microvilli, and presumably, stereocilia. The mutation of POLD1 cause dysfunction of DNA polymerase. EphA2 binds to pendrin, the major cause of deafness, and define the localization of the complex.

Academic Significance and Societal Importance of the Research Achievements

難聴の有病率は全ての疾病の中で2番目に高く、日常生活に支障を来す障害の原因として成人発症の難聴がトップで、かつその負担は今後さらに増加すると見込まれている(WHO, 世界疾病調査)。しかし根本的治療法がなく、多くの患者が重いハンデを背負いその社会的損失は計り知れない。難聴の病態、さらに言えば聴覚受容の分子機構には不明な点が多く、これが治療法の開発を困難としている。本研究成果は内耳がいかに音を感じるのかを分子レベルで解明するものである。かつ各分子はヒト遺伝性難聴の原因遺伝子として同定したもので、これらの知見はヒトの難聴の病態に直接応用できるものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (26 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (17 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] National institutes of health(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] POLD1 variants leading to reduced polymerase activity can cause hearing loss without syndromic features2020

    • Author(s)
      Doo-Yi Oh, Yoshihiro Matsumoto, Shin-ichiro Kitajiri, Nayoung K.D. Kim, Min Young Kim, Ah Reum Kim, Mingyu Lee, Chung Lee, Alan E. Tomkinson, Tatsuya Katsuno, So Young Kim, Hyun-Woo Shin, Jin Hee Han, Seungmin Lee, Woong-Yang Park, Byung Yoon Choi
    • Journal Title

      Human Mutation

      Volume: 41 Issue: 5 Pages: 913-920

    • DOI

      10.1002/humu.23984

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome2020

    • Author(s)
      Li, Nishio, Naruse, Riddell, Sapski, Katsuno, Hikita, Mizapourshafiyi, Smith, Cooper, Lee, Asano, Boettger, Kruger, Wietelmann, Graumann, Day, Boyd, Offermanns, Kitajiri, Usami, Nakayama
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1343-1343

    • DOI

      10.1038/s41467-020-15198-9

    • NAID

      120006888459

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detailed Clinical Features of Deafness Caused by a Claudin-14 Variant2019

    • Author(s)
      Tomohiro Kitano, Shin-ichiro Kitajiri, Shin-ya Nishio and Shin-ichi Usami
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 20 Issue: 18 Pages: 4579-4579

    • DOI

      10.3390/ijms20184579

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss2019

    • Author(s)
      Sugiyama、Moteki、Kitajiri、Kitano、Nishio、Yamaguchi、Wakui、Abe、Ozaki、Motegi、Matsui、Teraoka、Kobayashi、Kosho、Usami
    • Journal Title

      Genes

      Volume: 10 Issue: 9 Pages: 715-732

    • DOI

      10.3390/genes10090715

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential disruption of autoinhibition and defect in assembly of cytoskeleton during cell division decide the fate of human DIAPH1-related cytoskeletopathy2019

    • Author(s)
      Kim Bong Jik、Ueyama Takehiko、Miyoshi Takushi、Lee Seungmin、Han Jin Hee、Park Hye-Rim、Kim Ah Reum、Oh Jayoung、Kim Min Young、Kang Yong Seok、Oh Doo Yi、Yun Jiwon、Hwang Sang Mee、Kim Nayoung K D、Park Woong-Yang、Kitajiri Shin-ichiro、Choi Byung Yoon
    • Journal Title

      Journal of Medical Genetics

      Volume: 56 Issue: 12 Pages: 818-827

    • DOI

      10.1136/jmedgenet-2019-106282

    • NAID

      120007032326

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TRIOBP-5 sculpts stereocilia rootlets and stiffens supporting cells enabling hearing2019

    • Author(s)
      Katsuno Tatsuya、Belyantseva Inna A.、Cartagena-Rivera Alexander X.、Ohta Keisuke、Crump Shawn M.、Omori Koichi、Ito Juichi、Frolenkov Gregory I.、Friedman Thomas B.、Kitajiri Shin-ichiro
    • Journal Title

      JCI Insight

      Volume: 4 Issue: 12 Pages: 1-21

    • DOI

      10.1172/jci.insight.128561

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microarray analyses of otospheres derived from the cochlea in the inner ear identify putative transcription factors that regulate the characteristics of otospheres.2017

    • Author(s)
      Takehiro Iki, Michihiro Tanaka, Shin-ichiro Kitajiri, Tomoko Kita, Yuri Kawasaki, Akifumi Mizukoshi, Wataru Fujibuchi, Takayuki Nakagawa, Tatsutoshi Nakahata, Juichi Ito, Koichi Omori, Megumu K. Saito
    • Journal Title

      PLoS One

      Volume: 12

    • NAID

      120006782202

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Splice Site Mutation of Myosin VI in Mice Leads to Stereociliary Fusion Caused by Disruption of Actin Networks in the Apical Region of Inner Ear Hair Cells2017

    • Author(s)
      Yuta Seki, Yuki Miyasaka, Sari Suzuki, Kenta Wada, Shumpei P. Yasuda, Kunie Matsuoka, Yasuhiro Ohshiba, Kentaro Endo, Rie Ishii, Hiroshi Shitara, Shin-ichiro Kitajiri, Naomi Nakagata, Hirohide Takebayashi, Yoshiaki Kikkawa
    • Journal Title

      PLoS One

      Volume: 12

    • NAID

      120007099799

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Clinical Features of Deafness Caused by a Novel CLDN14 Variant2020

    • Author(s)
      Tomohiro Kitano, Shin-ichiro Kitajiri, Shin-ya Nishio, Shin-ichi Usami
    • Organizer
      ARO The 43rd Annual MidWinter Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of TRIOBP-5 in Stereocilia Rootlet Formation and Implications for Presbycusis and Gene Therapy2020

    • Author(s)
      Belyantseva, Katsuno, Cartagena-Rivera, Ohta, Petralia, Ono, Tona, Imtiaz, Kiyonari, Fitzgerald, Abe, Ikeya, Fenollar-Ferrer, Segawa, Omori, Ito, Frolenkov, Kitajiri, Friedman
    • Organizer
      ARO The 43rd Annual MidWinter Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of Hearing-loss Associated Mutations in MYO6 and In Vitro Functional Analysis2020

    • Author(s)
      Timothy F. Day, Shin-ichiro Kitajiri, Shin-ichiro Oka, Hideaki Moteki, Shin-ya Nishio, Shin-ichi Usami
    • Organizer
      ARO The 43rd Annual MidWinter Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト遺伝性難聴より見出したMYO6遺伝子変異の細胞学的解析2019

    • Author(s)
      北尻真一郎、Timothy Day、岡晋一郎、西尾信哉、宇佐美真一
    • Organizer
      第29回 日本耳科学会 総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 日本人で初めて見出された CLDN14 変異による難聴症例2019

    • Author(s)
      北野友裕、北尻真一郎、西尾信哉、宇佐美真一
    • Organizer
      第29回 日本耳科学会 総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ACTG1変異による難聴症例の臨床像と変異型γアクチンの細胞内局在2019

    • Author(s)
      宮嶋 宏樹(Hiroki Miyajima)、茂木 英明(Hideaki Moteki)、Timothy Day、西尾 信哉(Shin-ya Nishio)、北尻 真一郎(Shin-ichiro Kitajiri)、宇佐美 真一(Shin-ichi Usami)
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CNVs スクリーニングにより見出された OTOA 遺伝子変異による難聴 5 症例2019

    • Author(s)
      杉山 健二郎(Kenjiro Sugiyama)、北野 友裕(Tomohiro Kitano)、西尾 信哉(Shin-ya Nishio)、北尻 真一郎(Shin-ichiro Kitajiri)、茂木 英明(Hideaki Moteki)、宇佐美 真一(Shin-ichi Usami)
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Molecular investigations of deafness-related genes ACTG1 and MYO6 in vitro2019

    • Author(s)
      Day Timothy,岡 晋一郎,宮嶋宏樹, 北尻真一郎,西尾信哉,宇佐美真一
    • Organizer
      第64回日本聴覚医学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 内耳有毛細胞の感覚毛の根の形成および聴覚におけるアクチン束化タンパク質TRIOBPの役割2019

    • Author(s)
      勝野, Belyantseva, Cartagena-Rivera, 太田, Crump, Petralia, 小野, 十名, Imtiaz, Rehman, 清成, 金子, Wang, 阿部, 池谷, Fenollar-Ferrer, Riordan, Wilson, Fitzgerald, 瀬川, 大森, 伊藤, Frolenkov, Friedman, 北尻
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TRIOBP regulates the localization of molecules in the inner ear hair cell2018

    • Author(s)
      Shin-ichiro Kitajiri, Tomoko Kita, Raj K Ladher, Shin-ichi Usami
    • Organizer
      Joint Annual Meeting of 51st JSDB and 70th JSCB
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いたミトコンドリア1555変異難聴の病態解明2018

    • Author(s)
      喜多知子、伊木健浩、水越彬文、宇佐美真一、北尻真一郎
    • Organizer
      第28回日本耳科学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] OTOF遺伝子p.R1172Q変異による難聴発症機序の解析2018

    • Author(s)
      岩佐陽一郎、北尻真一郎、西尾信哉、吉村豪兼、宇佐美真一
    • Organizer
      第63回日本聴覚医学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ACTG1遺伝子変異による難聴症例の検討2018

    • Author(s)
      宮嶋宏樹、茂木英明、北尻真一郎、西尾信哉、村田考啓、池園哲郎、武田英彦、阿部聡子、岩崎聡、高橋優宏、内藤泰、山崎博司、神田幸彦、宇佐美真一
    • Organizer
      第63回日本聴覚医学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] An Attempt to Establish In Vitro Model Using TRIOBP KO Induced Pluripotent Stem Cells2017

    • Author(s)
      Hiroe Ohnishi、Shin-ichiro Kitajiri、Xiangxin Lou、Akiko Taura、Mirei Taniguchi、Fumi Ebisu、Tatsunori Sakamoto、Norio Yamamoto、Juichi Ito1、Koichi Omori、Takayuki Nakagawa
    • Organizer
      1st International Symposium on Inner Ear Therapies, November 01-03, 2017. Marrakech, Morocco
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝性難聴DFNA1の原因遺伝子DIAPH1と、その変異による難聴発症メカニズムの解明2017

    • Author(s)
      北尻真一郎、二之湯弦、西尾信哉、三好拓志、鳥居紘子、西村幸司、菅原一真、坂田英明、Dean Thumkeo、坂口博史、渡邊直樹、宇佐美真一、齋藤尚亮、上山健彦
    • Organizer
      日本人類遺伝学会第62回大会. 2017年11月15日(水)~18日(土)、神戸
    • Related Report
      2017 Annual Research Report
  • [Presentation] 不動毛の「根」の低形成と難聴2017

    • Author(s)
      北尻真一郎、伊藤壽一
    • Organizer
      第27回日本耳科学会. 2017年 11月22日(水)~ 24日(金)、横浜
    • Related Report
      2017 Annual Research Report
  • [Presentation] 内耳感覚毛の「根」の形成および維持におけるTRIOBPアイソフォームの役割2017

    • Author(s)
      Tatsuya Katsuno, Keisuke Ohta. Makoto Ikeya, Kazuya Ono, Koichi Omori, Juichi Ito, Shin-ichiro Kitajiri
    • Organizer
      第40回日本分子生物学会年会(2017年度生命科学系学会合同年次大会). 2017年12月6日~9日、神戸ポートアイランド
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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