中国人可疑遗传性视神经萎缩患者线粒体DNA分析及临床特征  

Mitochondria DNA mutation detection and clinical features in Chinese patients with suspected hereditary optic atrophy

作　　者：谢玥[1,2,3] 陈洁琼[1,2,3] 许可[1,2,3] 刘丽娟[1,2,3] 张晓慧[1,2,3] 蒋凤[1,2,3] 董冰[1,2,3] 李杨[1,2,3] 

机构地区：[1]首都医科大学附属北京同仁医院 [2]北京同仁眼科中心 [3]北京市眼科研究所 眼科学与视觉科学北京市重点实验室,100005

出　　处：《眼科》2015年第2期85-89,共5页Ophthalmology in China

基　　金：北京市卫生系统高层次卫生技术人才项目(2013-2021)

摘　　要：目的报告中国人可疑Leber遗传性视神经病变（LHON）患者线粒体DNA（mtDNA）基因突变的检测比例、突变特点及携带LHON基因突变患者的临床特征。设计回顾性病例系列。研究对象2006-2014年北京同仁医院可疑遗传性视神经萎缩患者909例，其中226例家族史明确，683例为散发患者。方法用PCR扩增DNA测序方法对909例患者及部分家系成员进行LHON线粒体DNA基因的16个原发突变检测，记录LHON患者的临床特征。主要指标mtDNA突变，突变检出率，发病年龄，视力，眼底改变。结果909例患者中432例携带LHON的mtDNA原发突变，阳性突变检出率为47．52％。369例（85．42％）患者携带LHON3点常见原发突变，其中294例（68．06％）携带m．11778G〉A，58例（13．43％）携带m．14484T〉C，17例（3．94％）携带m．3460G〉A；其余44例（10．18％）携带10种罕见突变（m．3635G〉A、m．3733G〉A、m．3736G〉A、m．3866T〉C、m．4171C〉A、m．10680G〉A、m．11696A〉G、m．14459G〉A、m．14482C〉G、m．T14502T〉C）；19例（4．40％）患者同时携带2点原发致病突变。LHON阳性患者发病年龄（18．53±9．31）岁（3-66岁）。LHON患者logMAR视力（1．36±0．68）。结论LHON是国人主要的遗传性视神经萎缩类型，不明原因视力下降者进行mtDNA基因突变分析十分重要。国人G3460A突变频率低。Objective To report the mutation ratio, mutation feature and corresponding clinical manifestations of Leber hereditary optic neuropathy（LHON） in Chinese patients with suspected hereditary optic atrophy. Design Retrospec- tive case series. Participants Nine hundred and nine probands who have been suspected as LHON from 2006 to 2014 col- lected at our laboratory. Methods Sixteen primary LHON-causing mtDNA mutations were screened by PCR-based sequenc- ing methods for all participants and some family members. The clinical features of LHON patients were recorded. Main Outcome Measures mtDNA mutation family medical history, visual acuity and fundus photography. Results Molecular defect in 432 （47.52%） of the 909 probands screened was detected. Among these, 369 patients （85.42%） were caused by m.l1778G〉A（294/432, 68.06%）, m.14484T〉C（58/432, 13.43%） or m.3460G〉A（17/432, 3.94%）. And 10 rare primary mtD- NA mutation （m.3635G〉A, m.3733G〉A, m.3736G〉A, m.3866T〉C, m.4171C〉A, m.10680G〉A, m.l1696A〉G, m.14459G〉A, m.14482C〉G, m.T14502T〉C） were found in 44 patients（10.18%）. The other 19 （4.40%） patients were carrying two primary mtDNA mutations. The mean onset age of visual loss was 18.53±9.31 years （ranging from 3-66 years）. The mean logMAR visual acuity for the probands carrying LHON-causing mtDNA mutations was 1.36±0.68. Conclusion LHON is a major type of Chinese hereditary optic atrophy. It is important to perform a mtDNA gene test for patients with unexplained decreased visual acuity. The mutation frequency of m.3460G〉A is low in Chinese.

关 键 词：LEBER遗传性视神经病变 视神经萎缩 MTDNA突变 

分 类 号：R774.63[医药卫生—眼科]