常染色体显性遗传性听神经病家系候选致病基因突变筛查  

Mutational analysis of candidate genes in a Chinese pedigree with dominantly inherited auditory neuropathy

作　　者：卢新红[1] 陈睿春[1] 鲁雅洁[2] 魏钦俊[2] 陈智斌[1] 曹新[2] 邢光前[1] 

机构地区：[1]南京医科大学第一附属医院耳鼻咽喉科,南京210029 [2]南京医科大学生物技术系

出　　处：《临床耳鼻咽喉头颈外科杂志》2012年第10期455-458,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：国家自然科学基金(No:31171217)

摘　　要：目的:了解DIAPH3基因以及25个已克隆的常染色体显性遗传非综合征型聋(DFNA)基因的已知突变是否与一个中国听神经病家系的发病有关。方法:以一个现存3代9人的常染色体显性遗传性听神经病核心家系为研究对象,对所有家系成员进行DIAPH3基因5′端非翻译区(5′UTR)的PCR扩增,1例听神经病患者进行DIAPH3、GJB2和GJB3基因全部编码区以及对其余23个DFNA基因的50个外显子进行PCR扩增,扩增产物经纯化后直接测序,筛查致病突变。结果:该家系未发现DIAPH3基因5′UTR的已知突变c.-172G>A和新的致聋突变,对GJB2、GJB3基因全部编码区及其余23个DFNA基因已知突变位点的筛查也无阳性发现。结论:结合前期工作,对照该家系成员DIAPH3基因及已克隆的25个DFNA基因的筛查结果,进一步提示该家系听神经病的发生可能是由新基因所致。Objective：Three genes including the OTOF, the DFNB59 and the DIAPH3 have been implicated previously in human non-syndromic auditory neuropathy. In this study, we aim to investigate whether DIAPH3 gene or the known deafness loci of 25 cloned autosomal dominant deafness （DFNA） genes contribute to the non- syndromic hearing loss of a Chinese pedigree with dominantly inherited auditory neuropathy （AN）. Method： Nine members of the kernal pedigree in this family were selected. Genomic DNA was isolated from the peripheral leukocytes of the subjects using the Puregene DNA Isolation Kits. Firstly, the 5＇UTR of DIAPH3 gene was PCR amplified in all subjects. Then, the DNA fragments spanning the entire coding regions of DIAPH3, GJB2 and GJB3 genes, and 50 exons in other 23 cloned DFNA genes were amplified using specific primers. Each fragment was pu-rified and analyzed by direct sequencing. The resultant sequence data were compared with the standard sequence to identify deafness-associated mutations. Result：PCR amplifications were successfully conducted. We failed to detect the presence either of c. -172G〉A mutation in the 5rUTR that have been reported, or any other deafness-associated mutations in the whole DIAPH3 gene, by sequence analysis. We also did not find any known deafness-causing mutations among the 25 cloned DFNA genes. Conclusion： The DIAPH3 gene, and the known deafness loci of 25 cloned DFNA genes seem not contribute to the pathogenesis of this Chinese AN family in this study, which suggesting new gene（s） involvement.

关 键 词：听神经病 DIAPH3基因 基因突变 常染色体显性遗传 

分 类 号：R764.4[医药卫生—耳鼻咽喉科]