基因芯片法检测自疑药源性耳聋患者基因突变35例

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (7): 768-771.

基因芯片法检测自疑药源性耳聋患者基因突变35例

魏绍煌¹, 郭舜民², 林文津²

¹福建医科大学附属第二医院药剂科,泉州 362000,福建
²福建省医学科学研究院,福建省医学测试重点实验室,福州 350001,福建

收稿日期:2011-04-18 修回日期:2011-05-30 出版日期:2011-07-26 发布日期:2011-09-22
通讯作者: 林文津,男,助理研究员,研究方向:药物不良反应及个体化用药。E-mail: lwjin@sina.com
作者简介:魏绍煌,男,主管药师,研究方向:医院药学。Tel: 15880918778 E-mail: weishaohuang@126.com
基金资助:
福建省自然科学基金资助项目(2010J01024);福建省科技厅省属公益院所基本专项资助项目(2011R1101024-2)

Analysis of gene mutation in 35 cases self-doubt hearing loss of patients related to drug-induced using DNA microarray

WEI Shao-huang¹, GUO Shun-min², LIN Wen-jin²

¹The Second Hospital Affiliated to Fujian Medical University, Quanzhou 362000, Fujian, China;
²Fujian Acadamy of Medical Sciences, Fujian Key Laboratory of Medical Measurement, Fuzhou 350001, Fujian, China

Received:2011-04-18 Revised:2011-05-30 Online:2011-07-26 Published:2011-09-22

摘要/Abstract

摘要： 目的: 对自疑药源性非综合征型耳聋患者进行中国人常见耳聋基因的突变分析,以明确其分子病因。方法: 收集35名自疑非综合征药源性耳聋患者的外周血样本,常规方法提取基因组DNA,进行基因芯片分析。对突变患者的基因,进行PCR 扩增,扩增产物经 DNA 测序分析,并与NCBI GenBank 数据库进行比对,从而对耳聋相关基因的突变进行分析。结果: 35名自疑非综合征耳聋患者中检出已知的mtDNA 12SrRNA 基因罕见致病突变C1494T 1例,占 2.86%,其余为野生型或是其他基因突变。结论: 在临床自疑药物性聋病患者中真正与线粒体基因突变相关的仅占少数, 48临床开展药源性耳聋基因检测时,最好同时进行其他耳聋相关基因的检测,而基因芯片检测是其中一项很好的方法。

关键词: 基因芯片, 测序法, 药源性耳聋, 线粒体基因, C1494T

Abstract: AIM: To investigate the gene mutation in self-doubt related to drug-induced hearing loss patients of non-syndromic sensorineural hearing loss and identify the molecular etiopathogenisis.METHODS: Peripheral blood samples were obtained from 35 cases self-doubt hearing loss of patients collected by out-patient clinic. Their genomic DNA was extracted from peripheral blood by extraction kits to undergo polymerase chain reaction, Gene microarray and sequencing so as to detect the mutations of mitochondrial 12S rRNA gene.RESULTS: In 35 patients, one mutation was found out in mtDNA 12S rRNA gene C1494T (2.86%), the other were wild type or other DNA mutations.CONCLUSION: Only a minority of drug-induced hearing loss associated with Mitochondrial DNA mutations amongst clinical self-doubt patients. The other deafness genes test simultaneously would be better. And gene microarray is one of a new and good method suggested.

Key words: Gene microarray, Drug-induced hearing loss, Self-doubt, 12S rRNA, C1494T

中图分类号:

R968

魏绍煌, 郭舜民, 林文津. 基因芯片法检测自疑药源性耳聋患者基因突变35例[J]. 中国临床药理学与治疗学, 2011, 16(7): 768-771.

WEI Shao-huang, GUO Shun-min, LIN Wen-jin. Analysis of gene mutation in 35 cases self-doubt hearing loss of patients related to drug-induced using DNA microarray[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 768-771.

参考文献

[1] 杨烨, 殷泽登. 线粒体DNA突变与氨基糖甙类抗生素致聋研究进展[J]. 中国耳鼻咽喉颅底外科杂志, 2010, 16(5):398-401.
[2] 何勇, 孙勃, 戴朴, 等. 福州市特教学校非综合征性聋分子病因学分析[J]. 中华耳科学杂志, 2006, 12(1):12-14.
[3] 林文津, 郭舜民, 张亚敏, 等. 聋病患者线粒体DNA突变检测在指导家系成员氨基糖苷类药物个体化使用中的应用[J]. 中国临床药理学与治疗学, 2008, 13(8):918-921.
[4] 李琦, 戴朴, 黄德亮, 等. 新疆药物性耳聋相关线粒体突变研究[J]. 中国听力语言康复科学杂志, 2008, (5):28-30.
[5] 李琦, 方如平, 黄德亮, 等. 新疆地区汉族和维吾尔族耳聋基因突变的比较研究[J]. 临床耳鼻咽喉头颈外科杂志, 2010, 24(1):11-15.
[6] 卜云飞, 吕晓光, 汪洋, 等. 22例非综合征型耳聋患者的致病基因突变位点分析[J]. 南京医科大学学报:自然科学版, 2010, 30(3):390-393.
[7] 王国建, 戴朴, 韩东一, 等. 基因芯片技术在非综合征性耳聋快速基因诊断中的应用研究[J]. 中华耳科学杂志, 2008, 6(1):61-66.
[8] 赵芳, 张芩娜. 一母系遗传氨基糖苷类抗生素致聋家系线粒体DNAA1555G 突变检测[J]. 中华耳科学杂志, 2010, 8(1):40-45.
[9] 赵钢涛, 杨凡, 许茜, 等. 基因芯片法检测遗传性耳聋相关基因[J]. 中国临床药理学与治疗学, 2010, 15(3):317-321.
[10] 张艳, 卞颖华, 许鹏飞, 等. 应用基因芯片技术检测非综合征型耳聋基因突变[J]. 生物技术通讯, 2010, 21(1):22-26.
[11] 袁永一, 黄德亮, 韩东一, 等. 实时荧光定量Taqman探针法检测线粒体 DNA1494C>T突变技术的建立及应用研究[J]. 听力学及言语疾病杂志, 2009, 17(2):180-182.
[12] 周学军, 欧阳小梅, 刘学忠. 常见遗传性聋致病基因研究进展及基因诊断的临床应用[J]. 听力学及言语疾病杂志, 2011, 19 (1):73-77.
[13] 管敏鑫, 邵敏华. 线粒体基因的分子诊断:早期氨基糖苷类抗生素耳毒作用的发现与预防[J]. 中国优生优育, 2008, 14(1):2-3.　
[14] Guan MX. Mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity[J]. Mitochondrion, 2011, 11(2):237-245.
[15] Zhao H, Li RH, Wang QJ, et al. Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494 T mutation in the mitochondrial 12S rRNA gene in a large Chinese family[J]. Am J Hum Genet, 2004, 74(1):139-152.
[16] Wang Q, Li QZ, Han D, et al. Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494 T mutation[J]. Biochem Biophys Res Commun, 2006, 340(2):583-588.
[17] Wang CY, Kong QP, Yao YG, et al. mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese[J]. Biochem Biophys Res Commun, 2006, 348(2): 712-715.
[18] Han DY, Dai P, Zhu QW, et al. The mitochondrial tRNAAla T5628C variant may have a modifying role in the phenotypic manifestation of the 12S rRNA C1494 T mutation in a large Chinese family with hearing loss[J]. Biochem Biophys Res Commun, 2007, 357(2):554-560.