Study of responsible genes for cochlea and cochlear nerve dysplasia

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659753
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: MATSUNAGA Tatsuo 独立行政法人国立病院機構(東京医療センター臨床研究センター), 聴覚障害研究室, 室長 (90245580)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Atsushi 岩手医科大学, いわて東北メディカル・メガバンク機構, 教授 (30327655) ; MIYA Fuyuki 独立行政法人理化学研究所, ゲノム医科学研究センター情報解析研究チーム, 研究員 (50415311) ; MUTAI Hideki 国立病院機構東京医療センター, 臨床研究センター・聴覚障害研究室, 研究員 (60415891) ; KUDOU Jun 慶応義塾大学, 医学研究科, 教授 (80178003) ; SUZUKI Naohiro 国立病院機構東京医療センター, 臨床研究センター, 研究員 (90611195)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 遺伝性難聴 / 蝸牛低形成 / 蝸牛神経低形成 / 次世代シーケンサー / エクソーム解析 / 新規疾患遺伝子

Research Abstract

Cochlea dysplasia and the associated feature, cochlear nerve dysplasia have been difficult to provide clinical treatment, while the cause of the diseases is largely unknown. We conducted whole exome analysis of the families associated with these symptoms by Next Generation Sequencer and identified 2 novel candidate responsible genes. A candidate gene X appeared to be expressed in cochlear nerve, and was suggested to associate with neurite extension in our immunohistochemical and in vitro studies. The other candidate gene Y has already been shown to have significant role in inner ear development in mouse model, and was finally suggested to cause cochlea dysplasia in human in this study. Our results expanded our understanding of molecular pathology of cochlea and cochlear nerve dysplasia and will lead to development of better diagnosis and treatment.

Research Products

• [Journal Article] 次世代シークエンサーを用いた難聴の遺伝子診断に関する検討 (2013)
  • Author(s): 松永達雄、鈴木直大、務台英樹、難波一徳、加我君孝
  • Journal Title: Otol Jpn Volume: 23(5) Pages: 903-907
  • Peer Reviewed
• [Journal Article] Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients : A cross-sectional, multi-center next-generation sequencing study (2013)
  • Author(s): Mutai H, Suzuki N, Shimizu A, Torii C, Namba K, Morimoto N, Kudoh J, Kaga K, Kosaki K, Matsunaga T
  • Journal Title: Orphanet J. Rare Dis Volume: 8(1) Pages: 172
  • Peer Reviewed
• [Journal Article] Cochlear nerve deficiency and associated clinical features in patients with bilateral and unilateral hearing loss (2013)
  • Author(s): Nakano A, Arimoto Y, Matsunaga T
  • Journal Title: Otol Neurotol Volume: 34(3) Pages: 554-558
  • Peer Reviewed
• [Journal Article] High prevalence of inner-ear and/or internal auditory canal malformations in children with unilateral sensorineural hearing loss (2013)
  • Author(s): Masuda S, Usui S, Matsunaga T
  • Journal Title: Int J Pediatr Otorhinolaryngol Volume: 77 Pages: 228-232
  • Peer Reviewed
• [Journal Article] Unilateral cochlear nerve hypoplasia in children with mild to moderate hearing loss (2012)
  • Author(s): Taiji H, Morimoto N, Matsunaga T
  • Journal Title: Acta Otolaryngol Volume: 132(11) Pages: 1160-7
  • Peer Reviewed
• [Journal Article] 側頭骨CTで両側蝸牛神経管狭窄を認めた小児難聴症例の検討 (2012)
  • Author(s): 仲野敦子、有本有季子、松永達雄、工藤典代
  • Journal Title: 日耳鼻会報 Volume: 115(9) Pages: 849-854
  • Peer Reviewed
• [Presentation] Rapid and efficient mutation detection in the hundreds of target genes by bench-top next generation sequencer with custom target capture method (2012)
  • Author(s): Shimizu A, Torii C, Suzuki N, Mutai H, Kudoh J, Kosaki R, Matsunaga T, Kosaki K
  • Organizer: 62nd Annual Meeting of the American Society of Human Genetics (ASHG)
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 20121106-10
• [Presentation] 蝸牛神経低形成例における聴覚所見 (2012)
  • Author(s): 泰地秀信、守本倫子、松永達雄
  • Organizer: 日本聴覚医学会第7回ERA・OAE研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-08
• [Remarks]
  • URL: http://www.kankakuki.go.jp/lab_c-1.html