KCNN4及KPTN基因在中国DFNA4型耳聋中的突变检测  

Detection of KCNN4 and KPTN gene mutations in Chinese DFNA4 family

作　　者：纵亮[1] 韩东一[1] 兰兰[1] 郭维维[1] 赵亚丽[1] 袁虎[1] 王秋菊[1,2] 

机构地区：[1]解放军总医院耳鼻咽喉头颈外科,解放军耳鼻咽喉研究所,北京100853 [2]国家人类基因组北方中心

出　　处：《中国耳鼻咽喉头颈外科》2006年第10期673-677,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：国家自然科学基金面上项目(30370782;30470956;30572016);北京市重大科技项目(H020220020610);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)联合资助

摘　　要：目的应用位置候选基因法了解中国DFNA4型耳聋家系定位区域内的两个基因KCNN4、KPTN与该家系耳聋表型的相关性。方法对一个6代相传、全基因组扫描连锁分析定位于DFNA4座位的常染色体显性遗传性耳聋中国家系成员,针对候选基因KCNN4、KPTN的全部编码序列设计引物,应用PCR扩增反应、产物纯化后直接测序的方法进行突变或多态性位点的检测与鉴定。结果两种基因的各对引物均有较好的扩增效果,直接测序结果与标准序列比对分析显示在KCNN4基因的所有编码区未检测到突变;在KPTN基因外显子10的编码区鉴定出一处同义突变(2154G／A,P302P),该突变不与家系的耳聋表型共分离,为已报道的单核苷酸多态性(SNP)位点(rs2293424)。结论该中国DFNA4家系的耳聋表型不是由其定位区域内的KCNN4、KPTN基因编码区的突变所导致,但这两个基因仍是极好的耳聋候选基因,其与遗传性耳聋的相关性有待进一步研究。OBJECTIVE To investigate whether the KCNN4 gene and KPTN gene contribute to a Chinese non-syndromic hearing loss pedigree linked to DFNA4 with positional candidate approach. METHODS The complete coding region of the two genes were amplified with polymerase chain reaction （PCR）, and bidirectional sequencing of the PCR products was subsequently applied in the 36 family members to identify the possible mutations or polymorphisms in the candidate genes. RESULTS Sequence analysis of coding regions and splice sites of the two candidate genes in 36 members including 12 hearing-impaired individuals in family Z002 failed to demonstrate any deafness-causing mutations of KCNN4 gene. There was one heterozygous mutation identified in exonl0 coding sequence （942C/T） of KPTN gene, which did not result in amino acid change （P302P） as a repoerted synonymous SNP site （rs2293424）. This SNP site did not cosegregate with the phenotype of family Z002. CONCLUSION Our study excluded the two candidates, KCNN4 and KPTN, as the causative genes involved in this Chinese DFNA4 pedigree. This work was supported by grants from the National High Tech Development Project （Grant No. 2004AA221080）, the National Natural Science Foundation of China （Grant Nos 30370782 and 30470956）, Beijing Science Technology Project （Grant No H020220020610）, the Foundation of National Excellent Doctoral Thesis （Grant No 2004No63） and Military Outstanding Expert Grant （Grant No 06J018）, [Key words]

关 键 词：聋 基因 突变 DFNA4型 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]