Deletion of a 4977-bp Fragment in the Mitochondrial Genome Is Associated with Mitochondrial Disease Severity

Large deletions in mitochondrial DNA (mtDNA) may be involved in the pathogenesis of mitochondrial disease. In this study, we investigated the relationship between a 4,977-bp deletion in the mitochondrial genome (ΔmtDNA(4977)) and the severity of clinical symptoms in patients with mitochondrial disease lacking known point mutations. A total of 160 patients with mitochondrial disease and 101 healthy controls were recruited for this study. The copy numbers of ΔmtDNA(4977) and wild-type mtDNA were determined by real-time quantitative PCR and analyzed using Spearman’s bivariate correlation analysis, t-tests, or one-way ANOVA. The overall ΔmtDNA(4977) copy number per cell and the proportion of mtDNA(4977) relative to the total wild-type mtDNA, increased with patient age and symptom severity. Surprisingly, the total mtDNA copy number decreased with increasing symptom severity. Our analyses revealed that increases in the proportion and total copy number of ΔmtDNA(4977) in the blood may be associated with disease severity in patients with mitochondrial dysfunction.