Study of responsible genes for cochlea and cochlear nerve dysplasia

耳蜗及耳蜗神经发育不良相关基因的研究

• 批准号: 24659753
• 负责人: MATSUNAGA Tatsuo
• 金额: $ 2.33万
• 依托单位: 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)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659753/
• 关键词: 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

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.

耳蜗发育不良及其相关特征，耳蜗神经发育不良一直难以提供临床治疗，而该病的病因在很大程度上尚不清楚。我们利用下一代测序仪对与这些症状相关的家族进行了全外显子组分析，并确定了2个新的候选责任基因。在我们的免疫组化和体外研究中，一个候选基因X似乎在耳蜗神经中表达，并被认为与轴突延伸有关。另一个候选基因Y已经在小鼠模型中被证明在内耳发育中起重要作用，并且在本研究中最终被认为是导致人类耳蜗发育不良的原因。我们的研究结果扩大了我们对耳蜗和耳蜗神经发育不良的分子病理学的理解，并将导致更好的诊断和治疗的发展。

项目成果

新生児・幼小児の難聴―遺伝子診断から人工内耳手術、療育・教育まで

新生儿和幼儿听力损失 - 从基因诊断到人工耳蜗植入手术、治疗和教育

• 发表时间: 2014
• 作者: 大友章子;南修司郎;永井遼斗;松永達雄;榎本千江子;藤井正人;加我君孝;坂田英明;加我君孝;加我君孝
• 通讯作者: 加我君孝

Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.

• DOI: 10.1186/1750-1172-8-172
• 发表时间: 2013-10-28
• 期刊: Orphanet journal of rare diseases
• 影响因子: 3.7
• 作者: Mutai H;Suzuki N;Shimizu A;Torii C;Namba K;Morimoto N;Kudoh J;Kaga K;Kosaki K;Matsunaga T
• 通讯作者: Matsunaga T

蝸牛神経低形成例における聴覚所見

耳蜗神经发育不全病例的听觉表现

• 发表时间: 2012
• 作者: 泰地秀信;守本倫子;松永達雄
• 通讯作者: 松永達雄

Target-captured next generation sequencing of reported deafness genes reveals variability of genetic background of hereditary hearing loss in Japan.

对报道的耳聋基因进行目标捕获的下一代测序揭示了日本遗传性听力损失遗传背景的变异性。

• 发表时间: 2013
• 作者: Mutai H;Suzuki N;Shimizu A;Torii C;Namba K;Kudoh J;Kosaki K;Matsunaga T
• 通讯作者: Matsunaga T

Rapid and efficient mutation detection in the hundreds of target genes by bench-top next generation sequencer with custom target capture method

通过具有定制目标捕获方法的台式下一代测序仪对数百个目标基因进行快速有效的突变检测

• 发表时间: 2012
• 作者: Shimizu A;Torii C;Suzuki N;Mutai H;Kudoh J;Kosaki R;Matsunaga T;Kosaki K
• 通讯作者: Kosaki K