散发高频听力下降人群中KCNQ4基因的突变筛查

Screening the Mutation of KCNQ4 Gene in Patients with High Frequencies Hearing Impairment

李丽娜;李庆忠;武文明;王秋菊;

1:解放军总医院第二附属医院耳鼻咽喉科

2:复旦大学附属眼耳鼻喉科医院

3:解放军总医院耳鼻咽喉-头颈外科

4:解放军总医院耳鼻咽喉研究所 (北京100091)

摘要
目的了解高频听力下降型感音性神经聋患者是否存在KCNQ4基因突变,并检测其是否存在与已知的KCNQ4相同的或者是新的基因突变,了解它们对高频听力下降发病机制的影响。方法在门诊收集散发高频听力下降型感音神经性聋患者71例,另外选取正常对照者40例。采取PCR扩增、直接测序的方法检测KCNQ4基因突变。结果KCNQ4基因中已经报道的和高频感音神经性听力损失有关的位点在实验组中未发现类似的突变,也没有发现可以引起氨基酸改变的新突变,只发现了几个多态性改变;在对照组中只发现了47bp的插入,没有发现47bp的缺失,也没有发现其他的多态性改变。结论KCNQ4基因的突变可能并不是引起散发高频听力下降的主要原因。
关键词
高频听力下降;KCNQ4;基因突变;筛查
基金项目(Foundation):
作者
李丽娜;李庆忠;武文明;王秋菊;
参考文献

1 Kubisch C,Schroeder BC,Friedrich T,et al.KCNQ4,a novel potas-siumchannel expressedinsensory outer hair cells,is mutatedin domi-nant deafness[J].Cell,1999,96:437.

2 Mhatre AN,Li J,Chen AF,et al.Genomic structure,cochlear expres-sion,and mutation screening of KCNK6,a candidate gene for DFNA4[J].J Neurosci Res,2004,75:25.

3 Robbins J.KCNQ potassiumchannels:physiology,pathophysiology,and pharmacology[J].Pharmacol Ther,2001,90:1.

4 Schroeder BC,Kubisch C,Stein V,et al.Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3K+channels causes epi-lepsy[J].Nature,1998,396:678.

5 Wollnik B,Schroeder BC,Kubisch C,et al.Pathophysiological mech-anisms of dominant andrecessive KVLQT1K+channel mutationsfound ininherited cardiac arrhythmias[J].HumMol Genet,1997,6:1943.

6 HeginbothamL,Lu Z,Abramson T,et al.Mutationsinthe K+chan-nel signature sequence[J].Biophys J,1994,66:1061.

7 Doyle DA,Cabral JM,Pfuetzner RA,et al.The structure of the potas-siumchannel:molecular basis of K+conduction and selectivity[J].Science,1998,280:69.

8 Russell MW,Dick M,Collins FS,et al.KVLQT1mutations in three families with familial or sporadic long QT syndrome[J].Hum Mol Genet,1996,5:1319.

9 Van Camp G,Coucke PJ,Akita J,et al.A mutational hot spot in the KCNQ4gene responsible for autosomal dominant hearing impairment[J].Hum Mutat,2002,20:15.

10 Perozo E,MacKinnon R,Vezanilla F,et al.Gating currents froma nonconducting mutant reveal open-closed conformations in shaker K+channels[J].Neuron,1993,11:353.

11 Coucke PJ,Van Hauwe P,Kelley PM,et al.Mutations in the KC-NQ4gene are responsiblefor autosomal dominant deafnessinfour DF-NA2families[J].Hum Mol Genet,1999,8:1321.

12 Talebizadeh Z,Kelley PM,AskewJW,et al.Novel mutation in the KCNQ4genein alarge kindred with dominant progressive hearingloss[J].Hum Mutat,1999,14:493.

13 Van Hauwe P,Coucke PJ,Ensink RJ,et al.Mutationsinthe KCNQ4K+channel gene,responsible for autosomal dominant hearing loss,cluster inthe channel pore region[J].AmJ Med Genet,2000,93:184.

14 王秋菊,曹菊阳,李宁,等.KCNQ4基因突变对常染色体显性遗传性聋家系的影响[J].中华耳鼻咽喉科杂志[J],2002,37:343.

本文信息

PDF(34K)

本文作者相关文章

李丽娜李庆忠武文明王秋菊