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Abstract：
Progressive external ophthalmoplegia (PEO), characterized by ptosis and impaired eye movements, is a clinical syndrome with an expanding number of etiologically distinct subtypes. Advances in molecular genetics have revealed numerous pathogenic causes of PEO, originally heralded in 1988 by the detection of single large-scale deletions of mitochondrial DNA (mtDNA) in skeletal muscle of people with PEO and Kearns-Sayre syndrome. Since then, multiple point variants of mtDNA and nuclear genes have been identified to cause mitochondrial PEO and PEO-plus syndromes, including mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and sensory ataxic neuropathy dysarthria ophthalmoplegia (SANDO). Intriguingly, many of those nuclear DNA pathogenic variants impair maintenance of the mitochondrial genome causing downstream mtDNA multiple deletions and depletion. In addition, numerous genetic causes of nonmitochondrial PEO have been identified.
摘要：
进行性外眼肌麻痹（PEO），以眼睑下垂和眼球运动受损为特征，是一种临床综合征，病因学上不同的亚型数量不断增加。分子遗传学的进展揭示了PEO的许多致病原因，最初是在1988年通过检测PEO和Kearns-Sayre综合征患者骨骼肌中线粒体DNA（mtDNA）的单个大规模缺失而宣布的。从那以后,已确定mtDNA和核基因的多个点变异导致线粒体PEO和PEO-plus综合征，包括线粒体神经胃肠脑肌病（MNGIE）和感觉共济失调性神经病构音障碍眼肌麻痹（SANDO）。有趣的是，许多这些核DNA致病变异会损害线粒体基因组的维持，导致下游mtDNA的多重缺失和耗竭。此外,已经确定了非线粒体PEO的许多遗传原因。
