中文摘要：

目的分析常染色体显性遗传性聋家系的听力学及遗传学表型特征，并鉴定其致聋基因。方法对一个常染色体显性遗传非综合征型感音神经性聋家系进行病史采集和听力学检测，绘制耳聋家系系谱图，提取受检者的基因组DNA；对先证者进行外显子组测序，并结合家系的遗传学特征及患病者的听力学特征等进行分析，应用Sanger测序对筛选出的候选变异位点进行验证。结果该家系共五代27人（男13人，女14人），现存19人；患感音神经性聋者10人，表型不确定者1人，现存明确感音神经性聋者7人，发病年龄10～30岁，均表现为双耳对称性进行性中度至重度感音神经性聋，听阈曲线为下降型或平坦型；共检测到6个已知耳聋基因的突变位点及900多个未知基因的变异位点，应用Sanger测序对检测到的EYA4（C．1486A〉T）、MY07A（c．3602G〉C）和ESPN（C．2225C〉T）已知耳聋基因的突变位点及DNMTl（c．4381C〉T）、BMP2（C．393A〉T）、TP63（C．854G〉A）和RAll（c．4162G~A）4个可疑的变异予以验证并排除了其致病的可能性。结论该家系符合常染色体显性遗传非综合征型聋遗传学特征，表现为中度至重度感音神经性聋；对已发现的3个已知耳聋基因突变位点及4个可疑的变异位点进行筛查，未发现明确的致病位点，提示其致聋基因可能为新的致聋基因；对于未知基因的鉴定，最好选取2个以上样本进行外显子组测序。

英文摘要：

Objective To analyze the genetic and clinical audiological characters of a Chinese family with au- tosomal dominant hereditary hearing loss, and to identify its causative gene. Methods The family tree was drawn based on medical history collection and clinical audiological characters. The whole exome sequencing was performed using the genome DNA of the proband, the sequencing data was analyzed according to the inheritance pattern ,some candidate mutation were confirmed by Sanger sequencing. Results There were 10 affected family members with au- tosomal dominant hereditary hearing loss, and 7 were affected individuals alive showed hearing impairment. Audio- logical assessments of the affected individuals revealed bilateral, progressive, moderate or severe sensorineural hear- ing losses. The Whole exome sequencing identified six known deafness gene mutations and many other variants, three possible candidates of the six mutations and four suspected variants have been tested in other members of this family and ruled out. Conclusion This family is characterized by autosomal dominant hereditary hearing loss,and its causative gene maybe a unknown one. Whole exome sequencing can identify the variants of known deafness genes,however, for the rapid screening of novel causative genes, it would be better to choose more than two samples to sequence.