与耳聋相关的线粒体tRNA突变  

Mitochondrial tRNA Mutations Associated With Hearing Loss

作　　者：郑静[1] 郑斌娇[1] 方芳[1] 朱翌[2] 吕建新[1] 管敏鑫[1,3] 

机构地区：[1]温州医学院Attardi线粒体生物医学研究院和浙江省医学遗传学重点实验室,温州325035 [2]温州医学院附属第一医院耳鼻喉科,温州325035 [3]Division of Human Genetics,Cincinnati Children's Hospital Medical Center,Cincinnati,Ohio 45229,USA

出　　处：《生物化学与生物物理进展》2012年第1期22-30,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81070794);国家重点基础研究发展计划(973)(2004CCA02200)资助项目;浙江省重大科技专项社会发展项目(2007C13021)~~

摘　　要：线粒体tRNA基因突变是导致感音神经性耳聋的原因之一.有些tRNA突变可直接造成耳聋的发生,称之为原发突变.如tRNALeu(UUR)A3243G等突变与综合征型耳聋相关,而tRNASer(UCN)T7511C等突变则与非综合征型耳聋相关.此外,继发突变如tRNAThr G15927A等突变则对原发突变起协同作用,影响耳聋的表型表达.这些突变可引起tRNA二级结构改变,从而影响线粒体蛋白质合成,降低细胞内ATP的产生,由此引起的线粒体功能障碍可导致耳聋的发生.主要讨论与耳聋相关的线粒体tRNA突变及其致聋机理.Mutations in the mitochondrial tRNAs are one of the causes of sensorineural hearing loss. Some tRNA mutations such as tRNALen（UUR） A3243G are associated with hearing impairment and other clinical symptoms, while other tRNA mutations including tRNA Ser（UCN） T7511C only produce the phenotype of hearing loss. These tRNA mutations are the primary factors for the development of hearing loss. On the other hand, other tRNA mutations such as tRNATM G15927A act in synergy with the primary tRNA mutations, modulating the phenotypic manifestation. The mutations alter the secondary structures of tRNAs, impair translation and decrease the ATP production. Consequently, mitochondrial dysfunctions caused by these tRNA mutations lead to hearing loss. It this review we summarize the deafness-associated mitochondrial tRNA mutations and discuss the pathophysiology of these mitochondrial tRNA mutations.

关 键 词：线粒体tRNA 耳聋 原发突变 继发突变 

分 类 号：Q75[生物学—分子生物学] R394[医药卫生—医学遗传学]