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

Yanchun Zhang; Yinan Ma; Dingfang Bu; Hui Liu; Changyu Xia; Ying Zhang; Sainan Zhu; Hong Pan; Pei Pei; Xuefei Zheng; Songtao Wang; Yufeng Xu; Yu Qi

doi:10.1371/journal.pone.0128624

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

PLoS One. 2015 May 29;10(5):e0128624. doi: 10.1371/journal.pone.0128624. eCollection 2015.

Authors

Yanchun Zhang¹, Yinan Ma¹, Dingfang Bu¹, Hui Liu², Changyu Xia³, Ying Zhang¹, Sainan Zhu⁴, Hong Pan¹, Pei Pei¹, Xuefei Zheng¹, Songtao Wang¹, Yufeng Xu¹, Yu Qi¹

Affiliations

¹ Department of Central Laboratory, Peking University First Hospital, No. 8, West District, Beijing, 100034, China.
² Department of Respiratory, Beijing Children's Hospital, Beijing, 100045, China.
³ Department of Clinical Laboratory, Peking University First Hospital, No. 8, West District, Beijing, 100034, China.
⁴ Department of Biostatistics, Peking University First Hospital, No. 8, West District, Beijing, 100034, China.

Abstract

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.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Base Sequence*
Child
Child, Preschool
DNA, Mitochondrial / genetics*
Genome, Mitochondrial*
Humans
Infant
Male
Metabolism, Inborn Errors / genetics*
Mitochondrial Diseases / genetics*
Sequence Deletion*
Severity of Illness Index

Substances

DNA, Mitochondrial

Grants and funding

This study was financially supported by grants from the National Natural Science Foundation of China (No. 81271256) and (No. 81471153) and Beijing Municipal Science & Technology Commission (No. Z131107002213062). The funders had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.