2例线粒体病患者的MT-ND6基因突变分析  

MT-ND6 gene mutation analysis in two Chinese patients with mitochondrial disease

作　　者：刘誉[1] 夏昌宇[2] 张英[3] 郑雪飞[3] 裴珮[3] 张惠丽[4] 马祎楠[3] 戚豫[3] LIU Yu XIA Chang-yu ZHANG Ying ZHENG Xue-fei PEI Pei ZHANG Hui-li MA Yi-nan QI Yu(Department of Pediatrics, Peking University First Hospital, Beijing 100034, China)

机构地区：[1]北京大学第一医院儿科,100034 [2]北京大学第一医院检验科,100034 [3]北京大学第一医院中心实验室,100034 [4]北京大学第一医院信息中心,100034

出　　处：《中国优生与遗传杂志》2017年第4期15-18,共4页Chinese Journal of Birth Health & Heredity

基　　金：国家自然科学基金(81271256);国家自然科学基金(81471153)

摘　　要：目的报道2例携带MT-ND6基因突变的线粒体病患者的临床和分子遗传学特点,探究线粒体DNA突变的致病机制。方法详细收集患者的临床资料,排除常见线粒体病突变位点(如A3243G,A8344G,T8993G/C,G13513A等)后,应用聚合酶链式反应-直接测序法分析16.6kb的线粒体基因组全序列,并应用Mito Tool在线软件进行氨基酸序列保守性分析,PROVEAN、SIFT和Poly Phen-2等软件进行错义突变的功能分析并判定突变性质。结果 2名先证者在ND6基因上各发现1个mt DNA变异,分别为G14453A和T14325C,二者均位于基因保守区,预测显示对蛋白功能有害,父母及100名健康对照中均未发现上述突变。结论 G14453A是MT-ND6基因上罕见的致病突变位点,该突变与MELAS综合征的发生密切相关;T14325C是LHON的可疑致病位点,但其致病性有待进一步研究。线粒体基因全测序不仅有助于常见线粒体病的临床诊断和产前筛查,还能提高一些临床表现不典型的线粒体病的分子诊断水平。Objective：To report the clinical and molecular genetic character of two Chinese mitochondrial patients with MT-ND6 mutation and explore the pathogenetic mechanism of mitochondrial DNA（mt DNA）mutation. Methods：The clinical information of patients was collected,and the common mt DNA mutations（such as A3243 G,A8344G,T8993G/C and G13513 A etc）were excluded. PCR-sequencing was used to analyze the whole-mitochondrial genome（16.6 kb）. Mito Tool was used to calculate the amino acid conservation rate,and PROVEAN,SIFT,Poly Phen-2 were used to predict and determine the function of missense mutation. Results：m.G14453 A and m.T14325 C mutation were found in proband 1 and proband 2 respectively,which both located in conserved region of MT-ND6. The in silico programs predicted that two mutations were ＂damaging＂. Both of them were not detected in their parents and 100 healthy controls. Conclusion：m.G14453 A is a rare pathogenic mutation in MTND6,which is related with MELAS.m.T14325 C is a candidate pathogenic mutation of LHON,however,the pathogenesis need to be studied further. The whole-mitochondrial gene sequencing has a significant application value in the diagnosis of mitochondrial disease,especially in some atypical and rare mitochondrial diseases.

关 键 词：MT-ND6基因 突变 线粒体DNA 线粒体病 

分 类 号：R746[医药卫生—神经病学与精神病学]