The clinical, myopathological, and genetic analysis of 155 Chinese mitochondrial ophthalmoplegia patients with mitochondrial DNA single large deletions

Mol Genet Genomic Med. 2024 Jan;12(1):e2328. doi: 10.1002/mgg3.2328. Epub 2023 Nov 28.


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.

Conclusion: 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.

Keywords: Kearns-Sayre syndrome; chronic progressive external ophthalmoplegia; mitochondrial DNA; single large-scale deletion.

MeSH terms

  • China
  • DNA, Mitochondrial / genetics
  • Gene Deletion
  • Humans
  • Kearns-Sayre Syndrome* / genetics
  • Kearns-Sayre Syndrome* / pathology
  • Ophthalmoplegia* / genetics
  • Ophthalmoplegia, Chronic Progressive External* / diagnosis
  • Ophthalmoplegia, Chronic Progressive External* / genetics
  • Ophthalmoplegia, Chronic Progressive External* / pathology
  • Retrospective Studies


  • DNA, Mitochondrial