Analysis of causative genes for mid-frequency hearing loss using next-generation sequencing

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H07404
• Research Category: Grant-in-Aid for Research Activity Start-up
• 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: YAMAMOTO Nobuko 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), その他部局等, 研究員 (90626897)
• Research Collaborator: MUTAI Hideki ; NARA Kiyomitsu ; HIROYASU Fumiko
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 谷型難聴 / MYO6 / POU4F3 / TECTA / 次世代シーケンサー / 遺伝性難聴

Outline of Final Research Achievements

In 95 families with non-syndromic bilateral mid-frequency sensorineural hearing loss, pathogenic or likely pathogenic variants were identified in 23 families, variants of unknown significance (VUS) were found in 38 families, and genetic causes were unknown in 34 families. Among 23 families for which a pathogenic variants was identified, MYO6 was causative gene in 6 families (26.1%) and POU4F3 was causative in 3 families (13.0%). In terms of 61 families including VUS, MYO6 variants were found in 12 families (19.7%) followed by TECTA in 7 families (11.5%). TECTA variants often can not be determined as pathogenic by only one family because obtaining accurate family history is difficult and most of TECTA variants with autosomal dominant inheritance are missense variants. For the future, data accumulation may change some VUS to pathogenic variants, which may increase the TECTA gene rate among mid-frequency hearing loss.

Free Research Field

遺伝性難聴

Academic Significance and Societal Importance of the Research Achievements

谷型難聴の原因遺伝子の変異スペクトラムと臨床像に関する検討はこれまでになく、初めて解明された。臨床では、遺伝カウンセリングに大変有用であり、治療法選択や進行性など予後の説明の際にも有用な情報である。さらに、谷型難聴における高頻度の原因遺伝子の発現機序を比較検討することで、谷型難聴の病態解明にもつなげられる可能性があり、有意義な結果である。