Elucidation of developmental mechanisms of the bilateral vestibular schwannoma in neurofibromatosis type 2 using patient-derived iPS cells

• Project/Area Number: 16K20276
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Keio University
• Principal Investigator: Matsuzaki Saeko 慶應義塾大学, 医学部(信濃町), 共同研究員 (70573400)
• Research Collaborator: OISHI Naoki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 神経線維腫症２型 / 聴神経腫瘍 / 遺伝性難聴 / NF２ / iPS細胞 / ヒトiPS細胞 / NF2 / ヒト疾患由来iPS細胞 / iPS / 神経線維腫症2型 / hiPS細胞 / 内耳道

Outline of Final Research Achievements

In the research of hereditary diseases with hiPS cells, repairing gene mutations is in general an indispensable step for confirming phenotypes at the cellular level. Therefore, in this study, we first identified mutations in the NF2 gene before establishing hiPS cells. DNA was extracted from the peripheral blood of 7 patients (3 males and 4 females) who had bilateral acoustic nerve tumors defined by MRI and were clinically diagnosed as NF2. Gene analysis was performed with a next-generation sequencer. Pathogenic variants were found in NF2 gene in 5 cases, likely pathogenic variant in 1 case. We are currently working on establishing patient-derived iPS cells from pathogenic mutant cases with severe symptoms.

Academic Significance and Societal Importance of the Research Achievements

神経線維腫症2型の患者由来iPS細胞を樹立するにあたり、まずは末梢血を用いてNF2患者の遺伝子変異の解析を行った。遺伝子変異と実際の臨床像を検討中であり、今回の研究成果により病原性の高い遺伝子変異症例を選択しiPS細胞を樹立することが可能となる。よってより効率的に神経線維腫症2型の病態を解明できると考えられる。

Research Products

• [Journal Article] Schwannoma of the External Auditory Canal as a Part of Schwannomatosis (2019)
  • Author(s): Saeko Matsuzaki, Naoki Oishi, Satoko Wakabayashi, Kaoru Ogawa
  • Journal Title: Acta Oto-Laryngologica Case Reports Volume: Vol. 4,Issue 1 Issue: 1 Pages: 5-9
  • DOI: 10.1080/23772484.2018.1563493
  • Peer Reviewed / Open Access
• [Journal Article] Expression Pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea. (2018)
  • Author(s): Saeko Matsuzaki, Makoto Hosoya, Hideyuki Okano, Masato Fujioka, Kaoru Ogawa
  • Journal Title: Neuroscience Letters Volume: 662 Pages: 185-188
  • DOI: 10.1016/j.neulet.2017.10.030
  • Peer Reviewed
• [Presentation] 当院の神経線維腫症２型症例におけるNF2遺伝子の分子遺伝学的検討 (2019)
  • Author(s): 野口勝, 藤岡正人, 松永達雄,大石直樹, 吉浜圭祐,西山崇経, 鈴木成尚, 細谷誠, 松崎佐栄子, 神崎晶,, 森本佑紀奈, 戸田正博, 大平貴之, 吉田一成, 小川郁
  • Organizer: 第28回日本聴神経腫瘍研究会
• [Presentation] 当院の神経線維腫2型症例におけるNF２遺伝子の分子遺伝学的検討 (2019)
  • Author(s): 野口勝, 藤岡正人, 大石直樹, 吉浜圭祐,松永達雄,務台英樹,奈良清光,西山崇経, 鈴木成尚, 細谷誠, 松崎佐栄子, 神崎晶,小川郁
  • Organizer: 第120回日本耳鼻咽喉科学会
• [Presentation] Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea (2018)
  • Author(s): Saeko Matsuzaki, Makoto Hosoya, Hideyuki Okano, Masato Fujioka, Kaoru Ogawa
  • Organizer: ARO 2018 Association for Research in Otolaryngology MidWinter Meeting
  • Int'l Joint Research
• [Presentation] コモンマーモセット蝸牛におけるEYA4発現パターンの検討 (2017)
  • Author(s): 松﨑 佐栄子、細谷 誠、藤岡 正人、小川 郁
  • Organizer: 第62回日本聴覚医学会
• [Presentation] EYA4遺伝子変異特異的疾患iPS細胞の樹立 (2017)
  • Author(s): 松﨑 佐栄子、細谷 誠、藤岡 正人、小川 郁
  • Organizer: 第27回日本耳科学会総会・学術講演会
• [Presentation] Canal wall down tympanoplasty with soft posterior meatal wall reconstruction in cases of recurrent cholesteatoma (2016)
  • Author(s): Saeko Matsuzaki
  • Organizer: 10ｔｈ International Conference on Cholesteatoma and Ear Surgery
  • Place of Presentation: Edinburgh International Conference Centre(イギリス エジンバラ)
  • Year and Date: 2016-06-05
  • Int'l Joint Research
• [Presentation] 真珠腫再形成性再発成人例に対する外耳道軟組織再建術の検討 (2016)
  • Author(s): 松崎 佐栄子
  • Organizer: 第117回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2016-05-19