Leber遗传性视神经病变患者G11778A位点突变与临床预后的关系

The relationship of visual prognosis and G11778A point mutation in Leber hereditary optic neuropathy

背景Leber遗传性视神经病变是一种典型的母系遗传性疾病，已经发现线粒体的多个突变可以导致该病的发生。目的报道2个携带线粒体G11778A位点突变的Leber遗传性视神经病变（LHON）家系及其临床预后。方法对在郑州大学第一附属医院眼科收集到的2个LHON家系40人进行家系分析和基因检测。2个家系成员中包括母系成员28人，其中LHON病患者10例，作为研究组，母系男性成员的后代及配偶2例作为对照组。抽取受试者外周血2ml，常规酚-氯仿-异戊醇法抽提外周血基因组DNA，应用逆转录聚合酶链反应（RT-PCR）扩增目的基因，对受试者基因进行测序，对3个常见突变位点G3460A、G11778A、T14484C进行检测和筛查。结果本研究中的2个家系所有母系成员（包括患者）均携带G11778A位点突变，家系内对照者未携带该突变位点。所有的家系成员未携带G3460A和T14484C位点的原发突变。这2个家系中的LHON患者视力均等于或低于0．1，未见有视力自行恢复者。结论本研究2个家系患者均携带G11778A点突变，视力预后较差。

Background Leber hereditary optic neuropathy （LHON） is a disease characterized by maternal inheritance. A number of mitoehondrial DNA （mtDNA） mutation has been thought to be associated with this disease. Objective This study was to investigate the clinical and molecular genetic properties of LHON in two Chinese families. Methods Forty subjects from two Chinese families with LHON were enrolled in Affiliated First Hospital of Zhengzhou University,including 28 maternal members （10 of these members arc LHON and 12 controls from two families. All the participants had a complete ophthalmic examination including visual acuity, direct ophthalmoscopy, color sensation and visual evoked potentials, MtDNA was extract from the whole blood sample of all participants. PCR- DNA sequencing was performed to detect the point mutation of the G11778A ,T14484C, and G3462A for each subject. Written informed consent was obtained from each subject prior to this study. Results Only Gl1778A point mutation was identified in all 28 maternal members from the two families. No point mutation of Gl1778A was identified in non-maternal members, and no point mutation of the T14484C and G3462A were found in the two families. Conclusions The inherited pattern of these two families shows typical clinical and genetic features of LHON. LHON patients with G11778A mutation have a poor prognosis of visual acuity.