中文摘要：

目的 对中国听神经病谱系障碍患者进行DIAPH3基因的筛查,了解中国听神经病谱系障碍人群中是否存在DIAPH3基因的新突变及热点突变位点,并结合临床表型与基因型进行研究,探讨DIAPH3基因相关的听神经病谱系障碍患者的临床遗传学特征。方法 选取2003—2013年我院确诊的并接受血样采集的125例听神经病谱系障碍患者,同时选取100例听力正常的健康志愿者作为对照。采集外周静脉血,提取基因组DNA,采用直接测序法进行DIAPH3基因突变的检测,选用DNAStar软件和Sequence Scanner软件进行序列比对分析。同时分析患者的临床特征,从临床表型与基因型两方面进行系统研究,探讨DIAPH3基因相关的听神经病谱系障碍患者的临床遗传学特征。结果 在125例听神经病谱系障碍患者中,共发现DIAPH3基因外显子区域的22处变异,包括可能致病突变7处（c.1425G〉A,c.1749T〉C,c.2605A〉C,c.-44C〉G,c.-179G〉A,c.-27C〉T和c.＊196A〉T）。结论 此7种突变均于中国听神经病谱系障碍人群中发现,在国内外尚未见报道,可能为听神经病谱系障碍相关的突变,有待于进一步的研究。

英文摘要：

Objective to identify DIAPH3 mutations in Chinese patients with auditory neuropathy spectrum disor- der（ANSD） and to investigate the clinical genetic characteristics of ANSD associated with DIAPH3. Methods We enrolled 125 patients with auditory neuropathy spectrum disorder diagnosed in our hospital from 2003 to 2013. The vein blood of the patients who provided an informed consent was collected and DNA was extracted. We designed 30 pairs of PCR primers according to the 29 exons of the DIAPH3 gene. Polymerase chain reaction （PCR） and direct sequencing was performed to identify mutations in the DIAPH3 gene, We screened the mutations ofDIAPH3 gene in the 125 ANSD patients, and also screened the novel mutations in 100 unrelated individuals with normal hearing. Finally, we analyzed the clinical features and genetic characteristics of the ANSD patients with DIAPH3 gene mutations. Results In this study, 22 variations in the exons of DI- APH3 gene were totally found in the 125 ANSD patients, including 7 possible pathogenic mutation（c. 1425G〉A, c. 1749T〉C, c.2605A〉C, c.-44C〉G, c.-179G〉A, c.-27C〉T and c.＊ 196A〉T）. Conclusion These 7 variations didn＇t exist in other ANSD patients, and the regions of the seven mutations are highly conserved across vertebrate apecies, so we considered that these seven mutations may had relationships with ANSD.