| Project/Area Number |
16K11176
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Research Collaborator |
Usami Shin-ichi
Nishio Shin-ya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 難聴 / 遺伝子 / 中耳奇形 / ANSD / エクソーム解析 / 遺伝子解析 / 遺伝学 / auditory neuropathy / マウス |
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| Outline of Final Research Achievements |
Middle ear anomaly can occur as a part of syndromic disorders, or as isolated defects. In this study, we performed whole exome sequencing analysis and data analysis was performed for a Japanese family with autosomal dominant nonsyndromic mixed hearing loss and middle ear anomaly without apparent microtia. Four potential causative variants, including a duplication variant in HOXA2, a deletion variant in MYCT1, and two non-synonymous missense variants were detected. Direct sequencing confirmed that all the four variants were segregated with hearing loss. Among these identified variants, we considered HOXA2 to be the most potential candidate causative gene. Direct sequencing analysis was also carried out to screen HOXA2 mutations for other 19 patients with middle ear anomaly or microtia, but no mutation was detected. HOXA2 mutations were reported to cause autosomal recessive or dominant microtia in three families, but hearing loss was less constantly recognized in the families.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により、遺伝的背景のほとんど明らかとなっていない遺伝性の中耳奇形に関して新規の原因遺伝子を同定することができた。このことは、今後の病態解明や治療法開発などに有用であるだけでなく、聴覚生理の理解の上でも重要な基盤となる。特に、見出された変異が転写因子であることより、発生の際にどのような役割を果たしているかの解明が期待される。
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