Department of Neurology, Peking University First Hospital, Beijing, China.
Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2328. doi: 10.1002/mgg3.2328. Epub 2023 Nov 28.
Progressive external ophthalmoplegia (PEO) is a common subtype of mitochondrial encephalomyopathy.
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.
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.
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.
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.
进行性眼外肌麻痹（PEO）是一种常见的线粒体脑肌病亚型。
本研究旨在探讨中国单一大片段线粒体 DNA（mtDNA）缺失导致 PEO 患者中线粒体 DNA 异常、肌肉病理学改变与临床表现之间的关系。
这是一项回顾性单中心研究。纳入了携单一大片段 mtDNA 突变的 PEO 患者，分析 mtDNA 缺失模式、肌病理改变与临床特征之间的相关性。
共纳入 155 例携带单一大型 mtDNA 突变的线粒体 PEO 患者，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 组的发病年龄为 9.61±4.12 岁，CPEO 组为 20.15±9.06 岁。mtDNA 缺失范围为 2225bp 至 9131bp，以 m.8470_13446del 最为常见。KSS 组的缺失长度长于 CPEO 组（p=0.004）。此外，KSS 组缺失的编码呼吸链复合亚单位基因（p=0.001）和 tRNA 基因（p=0.009）数量也更多。mtDNA 缺失大小与发病年龄呈弱负相关（p<0.001，r=-0.369）。肌纤维破碎红纤维、破碎蓝纤维和细胞色素 c 阴性纤维的比例与发病年龄无显著相关性（p>0.05）。然而，更多比例的异常肌纤维与运动不耐受、肢体肌无力、吞咽困难和小脑共济失调的发生率增加相关。
我们报告了一个由中国线粒体 PEO 患者组成的大型队列，他们携带有单一的大片段 mtDNA 缺失。我们的结果表明，mtDNA 缺失的长度和位置可能影响发病年龄和临床表型。肌肉病理学的严重程度不仅可以提示诊断，还可能与眼外肌以外的临床表现相关。
