Leber遗传性视神经病变家系tRNA GluA14683G突变的检测分析  

Detection and analysis of tRNAGlu A14683G mutations of pedigrees with Leber＇s hereditary optic neuropathy

作　　者：梁敏[1] 张娟娟[2] 刘晓玲[2] 瞿佳[1] 管敏鑫[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,325035 [2]温州医学院眼视光医院眼底病科 [3]浙江大学遗传学研究所

出　　处：《中华眼底病杂志》2013年第3期266-270,共5页Chinese Journal of Ocular Fundus Diseases

基　　金：浙江省教育厅科研项目（Y201017001）;温州市科技计划项目（Y20100272）

摘　　要：目的寻找与Leber遗传性视神经病变（LHON）相关的新突变位点。方法经临床检查确诊的2个LHON家系纳入研究。先证者及其他母系成员均进行详细的眼科检查。先证者发病年龄分别为7、14岁。358名健康成年人作为正常对照组。提取所有受检者外周血全基因组DNA；使用24对有部分重叠的引物对先证者行线粒体全序列扩增分析。同时对家系中其他母系成员及正常对照组进行线粒体DNA（mtDNA）检测。从GenBank中选取14种灵长类物种对线粒体序列进行种系发生学分析。结果mtDNA检测结果显示，家系中母系成员均未发现ND4G11778A、NDlG3460A、ND6T14484C原发性突变位点。全基因组扩增测序结果显示，2例先证者tRNAGlu 基因上存在未报道的A14683G同质性突变和多个多态性变异位点，分别属于东亚单体型Flal和G2。tRNAGlu A14683G位点位于线粒体tRNAGlu TψC茎上。该位点在14种灵长类物种高度保守，突变后增加了C-G的碱基配对。正常对照组中未发现该位点突变。结论tRNAGlu A14683G突变可能是与LHON相关的新突变。Objective To find the new mutations of Leber＇s hereditary optic neuropathy （LHON）. Methods Two LHON families were enrolled in this study. The probands and all maternal members in this two families were underwent ophthalmologic examinations. The ages of probands were seven and 14 years old respectively. A total of 358 healthy adults were enrolled in this study as control group. The genomic DNA from whole blood of participants were extracted. The entire mitochondrial genome of probands were PCR-amplified and sequenced in 24 overlapping fragments using primers as designed. At the same time, the mtDNA of maternal relatives and 358 controls were also detected. Fourteen primate species were selected from GenBank to analyzed the phylogenetics of mitochondrial sequence. Results There was no ND4 G11778A, ND1 G3460A, ND6 T14484C mutational site in all maternal members. Molecular analysis of mtDNA in this two families identified the homoplasmic tRNAGlu A14683G mutation and distinct set of variants belonging to the Asian haplogroup Flal and G2. The site was at theTψC-stem of tRNAGlu and extremely conserved among 14 primate species. It was anticipated that the A14683G increased the highly conserved C-G base-pairing. Furthermore, the A14683G was absence in control group. Conclusion The tRNAGlu A14683G mutation is likely a new mutation associated with LHON.

关 键 词：视神经萎缩 遗传性 LEBER 病因学 DNA 线粒体 突变 

分 类 号：R77[医药卫生—眼科]