遗传性耳聋相关基因SLC26A4新突变致病性分析  

Pathogenic analysis of a novel mutation of deafness gene SLC26A4

作　　者：高雪[1,2,3,4] 辛凤[1,2] 袁慧军[1,2] 戴朴[1,2,3] 

机构地区：[1]解放军总医院耳鼻咽喉头颈外科 [2]解放军总医院研究所,北京100853 [3]解放军总医院海南分院耳鼻喉科,三亚572013 [4]解放军第二炮兵总医院耳鼻喉科,北京100088

出　　处：《中华耳科学杂志》2014年第1期26-29,共4页Chinese Journal of Otology

基　　金：国家自然科学基金重点项目(81230020);“十二五”国家科技支撑计划重点项目(2012BAI12B00/2012BAI12B01);中国博士后科学基金面上资助(2012M21878),中国博士后科学基金特别资助(2013T60947);国家科技支撑计划课题(2012BAI09B02)

摘　　要：目的验证SLC26A4基因ivs16+10C>T变异与遗传性耳聋的相关性,确定其是否致病。方法我们采集了一个聋-聋婚配家庭中的2例样本(编号7518)、200例大前庭水管散发病例及200例正常听力对照的血液样本及临床资料,分析该变异在人群的携带情况。采用在线软件预测(Fruitfly)及RT-PCR法验证SLC26A4基因ivs16+10C>T变异是否对剪切位点的识别产生影响。结果 SLC26A4 ivs16+10C>T变异在中国人群中携带率低。在200例EVAS散发患者及200例正常人中检测,均未发现携带该变异。Fruitfly结果显示SLC26A4 ivs16+10C>T对剪切位点的识别没有影响,RT-PCR证实SLC26A4编码cDNA长度没有改变。结论 SLC26A4 ivs16+10C>T变异是非致病的核苷酸多态,推测7518家庭的后代不会复制父母的听力。Objective To analyze the pathogenesis of a novel mutation SLC26A4 ivsl6＋ 10C〉T detected in a Chinese family （No.7518）, and provide the basic information for the molecular diagnosis of genetic hearing loss. Methods Blood sam- ple and clinical data of family 7518, 200 sporadic EVAS （enlarge vestibular aqueduct syndrome） cases and 200 normal con- trol were collected. By splice site prediction and RT-PCR, we analyze the pathogenesis of SLC26A4 ivsl6＋ 10C〉T. Results According to Fruitfly, a change in the splice donor sequence from C to T in intron 16 of SLC26A4, is predicted to make no change in splice site recognition. RT-PCR results showed this mutation does not influence the length of mRNA. In addition, we identified SLC26A4 ivsl6＋ 10C〉T is rare in Chinese population. This mutation were absent in the 200 sporadic patients and 200 ethnicity-matched controls. Conclusion Our results demonstrated that SLC26A4 ivs 16＋ 10C〉T is not likely to be a pathogenic mutation. And their offspring will not replicate parents＇ hearing.

关 键 词：SLC26A4基因 ivsl6+10c〉T 致病性 大前庭水管综合征 

分 类 号：R349.6[医药卫生—基础医学]