Leber遗传性视神经病变研究进展和挑战.pdfVIP

HEREDITAS (Beijing) 2013 2 , 35(2): 123―135 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2013.00123 Leber 遗传性视神经病变研究进展和挑战 张阿梅, 姚永刚 , , 650223 Leber 遗传性视神经病变(Leber hereditary optic neuropathy, LHON; MIM535000)是最典型的线粒体遗传病 之一, 主要由线粒体DNA (Mitochondrial DNA, mtDNA)3 个原发突变(Primary mutation, m.11778GA 、m.3460G A 和 m.14484TC) 引起。患者表现为无痛性双侧视力下降或丧失, 主要易感人群为青壮年男性。不完全外显 (Incomplete penetrance)和性别偏好(Gender bias)是该病亟待解决的两大难题, 目前尚无有效的预防及治疗措施。 文章对近年来 LHON 的分子发病机制、临床症状及特点、体外实验和动物模型研究、预防及治疗等方面的研 究进展进行综述, 并集中介绍了我们近期对于我国LHON 患者的研究结果。 LHON; 线粒体DNA; 核基因; 功能验证 Research progress of Leber hereditary optic neuropathy ZHANG A-Mei, YAO Yong-Gang Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences Yunnan Province, Kunming Insti- tute of Zoology, Kunming 650223, China Abstract: Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.11778GA, m.3460GA and m.14484TC). Incomplete penetrance and gender bias are two riddles of this disease. Here we summa- rized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients. Keywords: LHON; mtDNA; nuclear genes; functional assay [1~4]