中文摘要：

目的 了解听神经病谱系障碍人群SLC17A8基因的突变携带情况,探讨SLC17A8基因与听神经病谱系障碍的相关性。方法 选取我院2003—2012年确诊的听神经病谱系障碍患者100例（前期工作筛查OTOF基因、PJVK基因、GJB2全基因、SLC26A4基因7＋8外显子IVS7＋2位点、线粒体基因1494及1555位点均为阴性）及100例听力正常的健康志愿者。针对SLC17A8基因的12个外显子设计19对引物,采用聚合酶链式反应进行目的片段扩增,并对PCR产物进行SLC17A8基因突变筛查,应用DNAStar软件进行测序结果的序列比对。同时对患者进行病史采集、体格检查及听力学检测。结果 100例听神经病谱系障碍患者中发现了SLC17A8基因外显子区域的变异12处,包括国际上尚未被报道且导致编码氨基酸改变的新突变1处、已知单核苷酸多态3处,以及位于3’端或5’端外显子非编码区的变异8处（6处为本研究首次报道）。1例女性听神经病谱系障碍患者携带c.824C〉A杂合突变,突变导致SLC17A8基因编码的囊泡谷氨酸转运体蛋白（VGLUT3）高度保守的囊泡内环状结构区的丙氨酸被天冬氨酸所替代（p.A275D）,而在100例听力正常的健康志愿者中均未发现该突变。结论 本研究在听神经病谱系障碍患者中发现SLC17A8基因的12处外显子区域变异及14处内含子区域变异,其中新发现的SLC17A8基因c.824C〉A突变可能导致VGLUT3向囊泡内转运谷氨酸的功能障碍而与听神经病谱系障碍发病相关。

英文摘要：

Objective To investigate variations of SLC17A8 gene in ANSD patients and analyze the possible association between the SLC17A8 gene and the patients with auditory neuropathy spectrum disorder（ANSD）. Methods We screened the genetic variants of SLC17A8 gene in 100 ANSD patients and 100 healthy unrelated individuals with normal hearing abilities （Control group）. All the patients were ascertained in our hospital from 2003 to 2012. 19 pairs of PCR primers were designed according to the 12 exons of SLC17A8 genome. Targeted fragments in SLC17A8 gene were amplified by polymerase chain reaction （PCR） and then the amplified target fragments were sequenced directly. All the ANSD patients were also investigated by history eolleetioning, physical examinationing and audiological examinationing. Results In this study, we found 12 varia- tions on the exons in SLC17A8 gene, including a novel missense variation, 3 previously reported single nucleotide polymor- phisms and 8 variations （6 variations were first reported） located on 5＂ non-coded region and 3＂ non-coded region. One fe- male patient with ANSD was detected a novel mutation （c.824C〉A） and the mutation was not found in the 100 healthy mem- bers. The nonpolar alanine is replaced by a polar aspartic acid （p.A275D） in the highly conserved middle cytoplasmic loop section of the VGLUT3 sequences. Conclusion In the present study, we found 26 variations of the SLC17A8 gene （14 variations in the introns） in 100 Chinese patients with ANSD. Our results suggest that the c.824C〉A variation is a novel possibly pathogenic variation in ANSD patients.