Comprehensive Genetic Analysis of Japanese Autosomal Dominant Sensorineural Hearing Loss Patients

• Project/Area Number: 17K16900
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Shinshu University
• Principal Investigator: Yoh-ichiro Iwasa 信州大学, 医学部, 助教(特定雇用) (10613002)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 遺伝子 / 難聴 / 常染色体優性遺伝 / 次世代シークエンサー / 先天性難聴 / ANSD / OTOF / ゲノム

Outline of Final Research Achievements

In general, autosomal dominant inherited hearing loss does not have a founder mutation, with the causative mutation different in each family. For this reason, there has been a strong need for efficient diagnosis methods for autosomal dominant sensorineural hearing loss (ADSNHL) patients. This study sought to verify the effectiveness of our analysis algorithm for the screening of ADSNHL patients as well as the usefulness of the massively parallel DNA sequencing (MPS). In this study, we analyzed seventy-five Japanese ADSNHL patients from 53 ENT departments nationwide participated in this study. We conducted genetic analysis of 75 ADSNHL patients using the Invader assay, TaqMan genotyping assay and MPS-based genetic screening. A total of 46 (61.3%) ADSNHL patients were found to have at least one candidate gene variant.

Academic Significance and Societal Importance of the Research Achievements

本研究により日本人難聴患者の原因遺伝子変異の種類や頻度を明らかにするとともに、どのような難聴を呈するかといった臨床的特徴を明らかにすることができた。特に、原因遺伝子の種類により聴力像が異なるという情報は、補聴器や人工内耳といった難聴に対する治療法を決める上で有用な情報として活用されることが期待される。

Research Products

• [Journal Article] A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations. (2020)
  • Author(s): Walls WD, Moteki H, Thomas TR, Nishio SY, Yoshimura H, Iwasa Y, et al
  • Journal Title: Hum Genet Volume: NA Issue: 10 Pages: 1315-1323
  • DOI: 10.1007/s00439-020-02174-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] OTOF mutation analysis with massively parallel DNA sequencing in 2,265 Japanese sensorineural hearing loss patients. (2019)
  • Author(s): Iwasa YI, Nishio SY, Sugaya A, Kataoka Y, Kanda Y, Taniguchi M, Nagai K, Naito Y, Ikezono T, Horie R, Sakurai Y, Matsuoka R, Takeda H, Abe S, Kihara C, Ishino T, Morita SY, Iwasaki S, Takahashi M, Ito T, Arai Y, Usami SI.
  • Journal Title: PLoS One. Volume: 14 Issue: 5 Pages: 0215932-0215932
  • DOI: 10.1371/journal.pone.0215932
  • Peer Reviewed / Open Access
• [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
• [Presentation] OTOF mutation analysis with massively parallel DNA sequencing in 2135 Japanese sensorineural hearing loss patients (2018)
  • Author(s): Iwasa Y, Usami S
  • Organizer: Association for Research in Otolaryngology 2018
• [Presentation] COL11A2遺伝子変異によるStickler症候群３型の２症例 (2017)
  • Author(s): 岡晋一郎、岩佐陽一郎、西尾信哉、茂木英明、宇佐美真一
  • Organizer: 第63回 日本聴覚医学会総会
• [Presentation] 次世代シーケンサーを用いたAuditory neuropathy spectrum disorderに対する遺伝子解析 (2017)
  • Author(s): 岩佐陽一郎、西尾信哉、宇佐美真一
  • Organizer: 第27回 日本耳科学会