Hong W J, Zheng B J, Qian J F, Wu H, Jin H, Zhu Y T
Department of Otorhinolaryngology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Jun 7;52(6):472-477. doi: 10.3760/cma.j.issn.1673-0860.2017.06.017.
Mutations in the mitochondrial DNA have been certified to be one of the most important causes of maternally inherited sensorineural hearing loss. Among these, mitochondrial 12S rRNA1555A>G, 1494C>T and other mutations are associated with both nonsyndromic and drug induced hearing loss caused by aminoglycosides. Individuals carrying 1555A>G or 1494C>T mutation have a variety of clinical manifestations, which implies that the 1555A>G or 1494C>T mutation is a chief factor underlying the development of deafness but insufficient to produce the clinical phenotype. Therefore other modifier factors, such as aminoglycosides, mitochondrial haplotypes, secondary mutation or nuclear modifier genes, may play an important role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA1555A>G or 1494C>T mutation. In this review, the modifier factors for the phenotypic expression of deafness-associated mitochondrial 12S rRNA1555A>G or 1494C>T mutations were summarized and proposed the pathogenesis of maternally inherited deafness.
线粒体DNA突变已被证实是母系遗传性感音神经性听力损失的最重要原因之一。其中,线粒体12S rRNA 1555A>G、1494C>T及其他突变与非综合征性和氨基糖苷类药物诱发的听力损失均有关联。携带1555A>G或1494C>T突变的个体有多种临床表现,这表明1555A>G或1494C>T突变是耳聋发生的主要因素,但不足以产生临床表型。因此,其他修饰因子,如氨基糖苷类药物、线粒体单倍型、二次突变或核修饰基因,可能在与耳聋相关的线粒体12S rRNA 1555A>G或1494C>T突变的表型表达中起重要作用。在本综述中,总结了与耳聋相关的线粒体12S rRNA 1555A>G或1494C>T突变表型表达的修饰因子,并提出了母系遗传性耳聋的发病机制。