摘要线粒体12S rRNA基因是引起氨基糖甙类抗生素耳毒性和非综合征型耳聋的突变热点区域。其中，位于高度保守的12S rRNA基因解码区的同质性1555A＞G和1494C＞T突变，可导致部分患者对氨基糖甙类抗生素超敏感。当发生1555A＞G或1494C＞T突变时，12S rRNA高度保守的A位就会形成新的1494C-G1555或1494U-A1555碱基配对，使得人类线粒体核糖体的结构与细菌核糖体更加相似，以致氨基糖甙类抗生素与12S rRNA的结合更加容易，从而解释了为何携带这些突变的个体在使用了氨基糖甙类抗生素后会出现或加重耳聋表型。相关功能研究表明，无论是否存在氨基糖甙类抗生素的作用，携带1555A＞G或1494C＞T突变的细胞均会出现线粒体蛋白合成缺陷，并随之引发细胞呼吸功能障碍。此外，携带这些突变的家系，其母系成员听力损失程度、发病年龄和外显率均存在较大差异，提示核修饰基因、线粒体单体型以及氨基糖甙类抗生素等对12S rRNA 1555A＞G和1494C＞T突变的表型表达起着修饰作用。这些研究成果为以下三个方面提供了科学依据：①预测个体耳毒性风险；②提高氨基糖甙类抗生素治疗的安全性；③降低耳聋发生率。

abstractsThe mitochondrial 12 S rRNA is a hot spot for mutations associated with both aminoglycoside-induced and nonsyndromic hearing loss. Of those, the homoplasmic 1555A ＞ G and 1494C ＞ T mutations at a highly conserved decoding region of the 12 S rRNA have been associated with hearing loss.These two mutations account for a significant number of cases of aminoglycoside ototoxicity. The 15 5 5 A ＞G or 1494C ＞ T mutation is expected to form novel 1494C-G1555 or 1494U-A1555 base-pair at the highly conserved A-site of 12S rRNA. These transitions make the human mitochondrial ribosome more bacteria-like, alter binding sites for aminoglycosides, thereby accounting for the fact that the exposure to aminoglycosides can induce or worsen hearing loss in individuals carrying one of these mutations.Biochemical characterization demonstrated an impairment of mitochondrial protein synthesis and subsequent defects in respiration in cells carrying the C1494T or A1555G mutation, in the presence or absence of aminoglycosides. Furthermore, a wide range of severity, age-at-onset and penetrance of hearing loss was observed within and among families carrying these mutations. Nuclear modifier genes, mitochondrial haplotypes and aminoglycosides should modulate the phenotypic manifestation of the 12 S rRNA 1555 A ＞ G and 1494C ＞ T mutations. Therefore, these data provide valuable information and technology to predict: ①which individuals are at risk for ototoxicity ; ② to improve the safety of aminoglycoside antibiotic therapy ;③ eventually to decrease the incidence of deafness..