背景:进行性眼外肌麻痹(PEO)是线粒体脑肌病的一种常见亚型。
目的:本研究旨在探讨线粒体DNA(mtDNA)异常之间的关系,肌肉病理学,以及以PEO表现的单个大规模mtDNA缺失的中国患者的临床表现。
方法:这是一项回顾性单中心研究。本研究包括在线粒体DNA中有单个大缺失的PEO患者。分析了mtDNA缺失模式之间的关联,肌肉病理学变化,和临床特征。
结果:总计,155例携带单个大规模mtDNA突变的线粒体PEO患者入组,包括137例慢性进行性眼外肌麻痹(CPEO)和18例Kearns-Sayre综合征(KSS)患者。KSS和CPEO的发病年龄分别为9.61±4.12和20.15±9.06。mtDNA缺失范围从2225bp到9131bp,与m.8470_13446del是最常见的。KSS组比CPEO组显示更长的缺失(p=0.004)。此外,在KSS组中,编码呼吸链复合物亚基(p=0.001)和tRNA基因(p=0.009)的缺失基因数量也较多.观察到mtDNA缺失大小与发病年龄之间的弱负相关(p<0.001,r=-0.369)。参差不齐的红色纤维的比例,参差不齐的蓝色纤维,细胞色素c阴性纤维与发病年龄没有显着相关(p>0.05)。然而,异常肌纤维的百分比较高对应于运动不耐受的患病率增加,四肢肌肉无力,吞咽困难,和小脑共济失调.
结论:我们报道了一个由线粒体PEO患者组成的大规模mtDNA缺失的大型中国队列。我们的结果表明,mtDNA缺失的长度和位置可能会影响发病年龄和临床表型。肌肉病理的严重程度不仅可以指示诊断,而且还可能与眼外肌以外的临床表现有关。
BACKGROUND: Progressive external ophthalmoplegia (PEO) is a common subtype of mitochondrial encephalomyopathy.
OBJECTIVE: The study aimed to investigate the relationship between mitochondrial DNA (mtDNA) abnormalities, muscle pathology, and clinical manifestations in Chinese patients with single large-scale mtDNA deletion presenting with PEO.
METHODS: This is a retrospective single-center study. Patients with PEO who had a single large deletion in mitochondrial DNA were included in this study. The associations were analyzed between mtDNA deletion patterns, myopathological changes, and clinical characteristics.
RESULTS: In total, 155 patients with mitochondrial PEO carrying single large-scale mtDNA mutations were enrolled, including 137 chronic progressive external ophthalmoplegia (CPEO) and 18 Kearns-Sayre syndrome (KSS) patients. The onset ages were 9.61 ± 4.12 in KSS and 20.15 ± 9.06 in CPEO. The mtDNA deletions ranged from 2225 bp to 9131 bp, with m.8470_13446del being the most common. The KSS group showed longer deletions than the CPEO group (p = 0.004). Additionally, a higher number of deleted genes encoding respiratory chain complex subunits (p = 0.001) and tRNA genes (p = 0.009) were also observed in the KSS group. A weak negative correlation between the mtDNA deletion size and ages of onset (p < 0.001, r = -0.369) was observed. The proportion of ragged red fibers, ragged blue fibers, and cytochrome c negative fibers did not correlate significantly with onset ages (p > 0.05). However, a higher percentage of abnormal muscle fibers corresponds to an increased prevalence of exercise intolerance, limb muscle weakness, dysphagia, and cerebellar ataxia.
CONCLUSIONS: We reported a large Chinese cohort consisting of mitochondrial PEO patients with single large-scale mtDNA deletions. Our results demonstrated that the length and locations of mtDNA deletions may influence onset ages and clinical phenotypes. The severity of muscle pathology could not only indicate diagnosis but also may be associated with clinical manifestations beyond the extraocular muscles.