摘要
背景：已发现线粒体tRNA（mt-tRNA）基因的突变与综合征和非综合征性听力损伤有关。然而，在听力损失的临床表达中mt-tRNA突变的病理生理学仍然知之甚少。 目的：本研究的目的是探讨mttRNA突变与听力损失之间的潜在关联。 方法和结果：我们在这里报告了母系传播非综合征性听力损失的谱系的分子特征。在12名母系亲属中，有5人患有不同程度的听力障碍，但他们都没有使用氨基糖苷类抗生素（AmAn）的病史。对来自母系亲属的完整线粒体基因组的遗传筛选鉴定了mt-tRNAHis G12192A和mt-tRNAThr G15927A突变的共存，以及属于人线粒体单倍群B5b1b的一组多态性。有趣的是，G12192A突变发生在mt-tRNAHis的TψC环的3''末端2-bp，其从各种物种进化保守。此外，众所周知的G15927A突变破坏了mt-tRNAThr的反密码子茎中高度保守的C-G碱基配对，可能导致mt-tRNA代谢失败。此外，从携带这些mt-tRNA突变的耳聋患者中分离的多核白细胞（PMNs）中观察到ATP产生显着减少和ROS产生增加，表明G12192A和G15927A突变可能导致线粒体功能障碍，耳聋。然而，GJB2，GJB3，GJB6和TRMU基因中不存在任何功能性突变/变体表明核基因可能在该家族中非综合征性听力丧失的临床表达中不起重要作用。 结论：我们的数据表明，mt-tRNAHis G12192A突变可能增加该家族中耳聋相关m-tRNAThr G15927A突变的外显率和表达能力。
关键词: 非综合征性听力损失，mt-tRNA突变，G12192A，G15927A，临床表现，病理生理学。
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