難聴遺伝子の解析による内耳聴覚・前庭の分子機構

通过听力损失基因分析内耳听力和前庭的分子机制

• 批准号: 13204024
• 负责人: 喜多村 健
• 金额: $ 3.2万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13204024/
• 关键词: 難聴; 遺伝子; ヒトゲノム; ミトコンドリア遺伝子

1.糸球体腎炎,先天性右耳瘻孔摘出手術の既往があり,オージオグラムでは右側に伝音難聴,左側は混合難聴を認め,左側は最大40dBの気骨導差を示すBOR症候群の症例を経験し,EYA1遺伝子変異の検索を施行した。その結果,エクソン7中の625番目の塩基がアデニンからグアニンへ変化し,コドン209でセリンからグリシンへ変化するミスセンス変異を認めた。2.110家系でGJB2遺伝子変異を検索し,12%の13家系で遺伝子変異を同定した。劣性遺伝家系が8家系,優性遺伝家系が2家系,弧発性が3家系であり,遺伝子変異は,235delCが61%と変異の中では最多を占めた。3.ミトコンドリア遺伝子変異を母系遺伝の難聴家系より同定した。さらに,ミトコンドリア遺伝子変異による難聴症例の側頭骨病理を報告し,内耳組織内の遺伝子変異の定量解析を行った。4.ミオシンVIIA遺伝子変異が既知のDFNA11家系において,詳細な聴覚検査を施行し,全例が左右対称性の両側感音難聴を呈し,1年に平均0.2から2.1dBの聴覚閾値の悪化がみられ,DFNA11家系はミオシンVIIA遺伝子変異の表現型としては中等度であると報告した。5.LacZをレポーターとしたトランスジェニックマウスのホモ接合体の内耳病理を解析し,聴覚閾値の上昇と相関したラセン神経節細胞の減少を同定した。一方,Six4遺伝子のノックアウトマウスの聴覚は正常で,行動異常もみられず,Six4遺伝子単独の変異は内耳機能に障害を与えないことを報告した。6.低音障害型難聴の優性遺伝家系を同定し,7名の対象者の末梢血よりDNAを採取した。

1. Due to spheroiditis, congenital right ear foramen extraction and manual surgery have been performed in the past, the right ear has a bad sound, the left has a mixed bone defect, the left has a maximum 40dB bone difference, and the BOR syndrome has a history of pain, and the EYA1 has a narrow band. According to the results, you can find out the results in this paper. The results show that there are some problems in the system, such as the number of items in 7, the number of items, and the number of items. 2.110 pedigrees were from GJB2 families, and 12% were from 13 pedigrees. 8 families of inferior sex family, 2 families of sex family, 3 families of arc sex family and 61% of 235delC family account for the most. 3. The child is the mother of the child, the mother is the mother, the family is the same. The report of bone pathology was reported, and the quantitative analysis was performed in the inner ear tissue. 4. It is known that DFNA11 pedigrees are suffering from diseases such as DFNA11 pedigrees, VIIA pedigrees, DFNA11 pedigrees, DFNA11 pedigrees and DFNA11 pedigrees. The inner ear pathology of the joint was analyzed by 5.LacZ. The inner ear pathology of the joint was analyzed. On the other hand, the Six4 operator is not responsible for the normal operation, while the Six4 operator is responsible for the failure of the internal earphone and the report report. 6. The pedigree of bass dyspnea was identified as the same, and the peripheral blood of 7 patients with bass disorder were collected by DNA.

项目成果

Tamagawa Y: "Nonsyndromic dominant hearing loss (DFNA11 ) caused by a myoisn VII A mutation"Laryngo scope. 112. 292-297 (2002)

Tamakawa Y：“由 myoisn VII A 突变引起的非综合征性显性听力损失（DFNA11）”喉镜。

Takago H.: "A vasoactive agent enhances the effect of ATP on cochlear blood flow"Acta Otolaryngol (Stockh). 121. 130-134 (2001)

Takago H.：“血管活性剂增强 ATP 对耳蜗血流的影响”Acta Otolaryngol (Stockh)。

Kamiya K: "Mitosis and apoptosis in postnatal auditory system of the C3H/He strain."Brain Res.. 901. 296-302 (2001)

Kamiya K：“C3H/He 品系出生后听觉系统的有丝分裂和细胞凋亡。”Brain Res.. 901. 296-302 (2001)

Ozaki, H.: "Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development"Mol.Cell.Biol.. 21. 3343-3350 (2001)

Ozaki, H.：“Six4，一种推定的肌生成素基因调节因子，对于小鼠胚胎发育不是必需的”Mol.Cell.Biol.. 21. 3343-3350 (2001)

Fukuda S: "A family affected by branchio-oto syndrome with EYA1 mutations."Auris Nasus Larynx. 28. S7-S11 (2001)

Fukuda S：“一个受 EYA1 突变的鳃耳综合征影响的家庭。”Auris Nasus Larynx。