95例前庭水管扩大核心家系SLC26A4基因特异突变图谱

A Distinct Spectrum of SLC26A4 Mutations in 95 Nuclear Families Associated with Enlarged Vestibular Aqueduct

赵亚丽;王秋菊;李庆忠;兰兰;袁虎;纵亮;韩明鲲;王大勇;翟所强;

1:解放军总医院耳鼻咽喉-头颈外科 解放军耳鼻咽喉科研究所

2:中国医学科学院中国协和医科大学基础医学研究所医学分子生物学国家重点实验室

3:解放军总医院耳鼻咽喉-头颈外科

4:解放军耳鼻咽喉科研究所

摘要
目的探讨中国人群中前庭水管扩大(enlarged vestibular aqueduct,EVA)患者SLC26A4基因突变图谱,为相关基因的筛查及临床应用奠定基础。方法采集95例EVA核心家系,募集84名听力正常者及46名内耳结构正常的听力损失患者作为对照。提取基因组DNA,应用聚合酶链反应(PCR)的方法扩增SLC26A4基因的21个外显子,纯化PCR产物后直接测序,使用DNAStar及BioEdit序列比对软件分析SLC26A4基因的突变位点,利用Clustal软件进行同源氨基酸序列比对分析。结果在95例EVA核心家系中,93例发生了SLC26A4基因突变,约占97.9%(93/95)。其中双等位基因突变占88.4%(84/95),单等位基因和未发现突变的家系分别占9.5%和2.1%。93个家系中共发现38种突变,包括23种国际上尚未报道的突变,15种已报突变(5种仅报道于中国家系)。IVS7-2A>G是所有突变中最常见的突变,其在所有突变体中约占57.63%(102/177),75(75/95)个家系发生了此种突变。结论95例中国EVA核心家系的SLC26A4基因调查中,发现了一个中国特异性的SLC26A4基因突变谱:97.9%的中国EVA患者均可检测到SLC26A4基因的突变,双等位基因突变率约为88.4%;23种新的突变和5种仅报道于中国家系的突变在其他人群未曾检测到;IVS7-2A>G为中国人群前庭水管扩大患者最常见的突变。
关键词
前庭水管扩大;SLC26A4;基因;突变
基金项目(Foundation):
国家863项目(2006AA02Z181);; 国家自然基金面上项目(30672310&30771203);; 高等学校全国优秀博士学位论文作者专项资金资助项目(200463);; 军队“十一五”杰出人才项目(06J018);; 北京市科技计划重大项目(D0906005040291);; 国家973项目(2007CB507400);; 北京重大专项课题项目(7070002);; 国家“十一五”科技支撑计划(2006BAI02B06&2007BAI18B12)
作者
赵亚丽;王秋菊;李庆忠;兰兰;袁虎;纵亮;韩明鲲;王大勇;翟所强;
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