线粒体tRNA^(Glu)A14693G可能是与Leber遗传性视神经病变相关的基因突变  

Leber’s hereditary optic neuropathy may be associated with the mitochondrial tRNA～(Glu) A14693G mutation in three Chinese families

作　　者：张永梅[1,2] 冀延春[1,2] 刘晓玲[2] 周翔天[2] 赵福新[2] 孙艳红[3] 韦企平[3] 张娟娟[2] 刘燕[1,2] 瞿佳[2] 管敏鑫[1,4,5] 

机构地区：[1]温州医学院浙江省医学遗传学重点实验室,温州325035 [2]温州医学院眼视光学院,温州325027 [3]北京中医药大学东方医院眼科,北京100078 [4]Division of Human Genetics,Cincinnati Children's Hospital Medical Center [5]Department of Pediatrics,University of Cincinnati College of Medicine

出　　处：《遗传》2010年第4期353-359,共7页Hereditas（Beijing)

基　　金：国家杰出青年科学基金;海外;港澳青年学者合作研究基金(编号:30628013);浙江省自然科学基金重大项目(编号:Z204492);浙江省自然科学基金项目(编号:Y2090649)资助

摘　　要：收集了3个具有典型临床特征的中国汉族Leber遗传性视神经病变(Leber′s hereditary optic neuropathy,LHON)家系。通过对先证者和家系其他成员进行眼科临床(如视力损害程度和发病年龄)检查,发现这些家系成员中视力损害的外显率很低,经mtDNA测序分析,在tRNAGlu上发现了A14693G同质性突变位点,多态性位点分别属于东亚单体型Y1b、Y1和Y1,没有发现其他高度保守和有功能意义的突变位点。A14693G突变位于线粒体tRNAGlu高度保守区(通用位点为54位),可能导致tRNA空间结构和稳定性发生改变,继而影响tRNA的代谢,导致线粒体蛋白合成功能受损和ATP障碍,最终导致视力损害。所以,tRNAGluA14693G突变可能是与视神经病变相关的致病性线粒体突变位点。We reported here the clinical,genetic and molecular characterization of three Han Chinese families with Le-ber’s hereditary optic neuropathy.Ophthalmologic examinations revealed the variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of these families.Strikingly,these families exhibited extremely low penetrances of visual impairment.Sequence analysis of complete mitochondrial genomes in these pedigrees identified the known homoplasmic tRNAG luA14693G mutation and distinct sets of polymorphism belonging to haplogroups Y1b,Y1 and Y1,respectively.The A14693G mutation occurs at the extremely conserved nucleotide（conventional position 54）of tRNA Glu .Thus,this mutation may alter structural formation and stabilization of functional tRNAs,thereby leading to a fail-ure in tRNA metabolism and mitochondrial dysfunction involved in visual impairment.However,none of other variants showed the evolutionary conservation and functional significance.These observations suggested that the tRNA Glu A14693G mutation may be involved in the pathogenesis of optic neuropathy in these families.

关 键 词：LEBER遗传性视神经病变 线粒体DNA 视力障碍 突变 

分 类 号：R774.6[医药卫生—眼科]