CAJ | 학술논문

线粒体DNA突变是引起感音神经性耳聋的重要原因之一,这些突变主要位于线粒体12SrRNA和tRNA基因上.其中12S rRNA基因上的同质性A1555G和C1494T突变与氨基糖甙类抗生素造成的耳聋相关.携带这两个突变的个体对耳毒性药物高度敏感,导致临床上常见的"一针致聋"现象.但携带A1555G或C1494T突变的个体在没用药的情况下也能产生非综合征型耳聋,而且同一家系内和不同家系间的母系成员在听力损失程度、发病年龄及听力曲线上存在很大差异.这些数据表明A1555G或C1494T突变是导致非综合征型耳聋发生的首要因子,其他修饰因子包括氨基糖甙类抗生素、线粒体DNA单倍型和核修饰基因等,在线粒体12S rRNA A1555G或C1494T突变相关的耳聋表型表达上起协同作用.作者简要介绍了这些因素对线粒体DNA突变致聋的影响以及母系遗传性耳聋发生的可能致病机制.
선립체DNA돌변시인기감음신경성이롱적중요원인지일,저사돌변주요위우선립체12SrRNA화tRNA기인상.기중12S rRNA기인상적동질성A1555G화C1494T돌변여안기당대류항생소조성적이롱상관.휴대저량개돌변적개체대이독성약물고도민감,도치림상상상견적"일침치롱"현상.단휴대A1555G혹C1494T돌변적개체재몰용약적정황하야능산생비종합정형이롱,이차동일가계내화불동가계간적모계성원재은력손실정도、발병년령급은력곡선상존재흔대차이.저사수거표명A1555G혹C1494T돌변시도치비종합정형이롱발생적수요인자,기타수식인자포괄안기당대류항생소、선립체DNA단배형화핵수식기인등,재선립체12S rRNA A1555G혹C1494T돌변상관적이롱표형표체상기협동작용.작자간요개소료저사인소대선립체DNA돌변치롱적영향이급모계유전성이롱발생적가능치병궤제.
Mutations in the mitochondrial DNA have been found to be one of the most important causes of sensorineural hearing loss. In particular, these mutations often occur in the mitochondrial 12S rRNA and tRNA genes. Of these, the homoplasmic A1555G and C1494T mutations in the 12S rRNA have been associated with both aminoglycoside induced and nonsyndromic hearing impairment in many families worldwide. Children carrying the A1555G or C1494T mutation are susceptible to the exposure of ototoxic drugs, thereby inducing or worsening hearing loss. Individuals harboring A1555G or C1494T mutation can also develop hearing loss even in the absence of aminoglycoside exposure. However, matrilineal relatives of intra-families or inter-families carrying the A1555G or C1494T mutation exhibit a wide range of severity,age-at-onset, and audiometric configuration of hearing impairment. These indicate that the A1555G or C1494T mutation is a primary factor underlying the development of deafness but insufficient to produce the clinical phenotype. Thus, other modifier factors, such as aminoglycoside (s), mitochondrial DNA haplotype(s) or nuclear modifier gene(s), play a role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA A1555G or C1494T mutation. In this review, we summarize the modifier factors for the phenotypic expression of deafness-associated 12S rRNA A1555G and C1494T mutations and propose the molecular pathogenetic mechanism of maternally inherited deafness.