Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity  

作　　者：Zewen Gao Ye Chen Min-Xin Guan 

机构地区：[1]Division of Clinical Genetics and Genomics,The Children's Hospital,Zhejiang University School of Medicine [2]Institute of Genetics,Zhejiang University and Department of Genetics,Zhejiang University School of Medicine

出　　处：《Journal of Otology》2017年第1期1-8,共8页中华耳科学杂志（英文版）

基　　金：supported by the project from National Basic Research Priorities Program of China (2014CB541702);National Natural Science Foundation of China (31671305)

摘　　要：Aminoglycosides(Am An) are widely used for their great efficiency against gram-negative bacterial infections. However, they can also induce ototoxic hearing loss, which has affected millions of people around the world. As previously reported, individuals bearing mitochondrial DNA mutations in the 12 S rRNA gene, such as m.1555A>G and m.1494C>T, are more prone to Am An-induced ototoxicity. These mutations cause human mitochondrial ribosomes to more closely resemble bacterial ribosomes and enable a stronger aminoglycoside interaction. Consequently,exposure to Am An can induce or worsen hearing loss in these individuals. Furthermore, a wide range of severity and penetrance of hearing loss was observed among families carrying these mutations. Studies have revealed that these mitochondria mutations are the primary molecular mechanism of genetic susceptibility to Am An ototoxicity, though nuclear modifier genes and mitochondrial haplotypes are known to modulate the phenotypic manifestation.Aminoglycosides(Am An) are widely used for their great efficiency against gram-negative bacterial infections. However, they can also induce ototoxic hearing loss, which has affected millions of people around the world. As previously reported, individuals bearing mitochondrial DNA mutations in the 12 S rRNA gene, such as m.1555A>G and m.1494C>T, are more prone to Am An-induced ototoxicity. These mutations cause human mitochondrial ribosomes to more closely resemble bacterial ribosomes and enable a stronger aminoglycoside interaction. Consequently,exposure to Am An can induce or worsen hearing loss in these individuals. Furthermore, a wide range of severity and penetrance of hearing loss was observed among families carrying these mutations. Studies have revealed that these mitochondria mutations are the primary molecular mechanism of genetic susceptibility to Am An ototoxicity, though nuclear modifier genes and mitochondrial haplotypes are known to modulate the phenotypic manifestation.

关 键 词：AMINOGLYCOSIDES OTOTOXICITY Genetic SUSCEPTIBILITY MITOCHONDRIAL DNA MUTATIONS 

分 类 号：R764[医药卫生—耳鼻咽喉科]