核修饰基因突变与线粒体基因突变协同致聋

Mutations of nuclear modified genes and mitochondrial genes cause deafness synergistically

很多因素,如氨基糖苷类抗生素、核修饰基因等,对mtDNA突变引起的遗传性聋都具有协同作用,影响耳聋的表型表达。现主要综述MTO1、GTPBP3、TRMU、TFB1M及YARS2五种核修饰基因突变协同mtDNA突变致聋的研究进展及可能致病机制。作为一个可能协同致聋的核修饰基因,致病性YARS2和肌病、乳酸性酸中毒与铁粒细胞性贫血(MLASA)临床三联征都有关,该突变会减弱线粒体tRNA^(Tyr)的氨基酰化能力。目前,对于该核修饰基因突变协同致聋的机制仍在探索当中。

Factors such as aminoglycoside antibiotics and nuclear modified genes have synergistic effects on genetic deafness caused by mtDNA mutations,and thus affect phenotypic presentation of deafness.Here we mainly discuss the process and probable mechanism of five nuclear modified genes（MT01,GTPBP3,TRMU,TFBIMand YARS2）,which cause deafness with mitochondria gene mutations synergistically.As a potential deafness factor,Y4RS2 gene mutations have been reported aassociated with myopathy,lactic acidosis,and iron squamous cell anemia（MLASA）,which will weaken the amino acylation ability of mitochondrial tRNA^Tyr.But now,the mechanism of cooperation between nuclear modified gene mutations and mitochondrial gene mutations still remains unknown.