Abstract
Abstract
Purpose
To describe a novel DNA2 variant contributing to defects in mtDNA maintenance and mtDNA depletion syndrome (MDS), and the clinical and histological findings associated with this variation.
Methods
Herein, we describe the case of a patient who presented with hearing loss and myopathy, given the family history of similar findings in the father, was evaluated by sequencing of the deafness gene panel, mitochondrial genome, and the exome. Furthermore, tissue staining, mtDNA copy number detection, mtDNA sequencing, and long-range polymerase chain reaction tests were also conducted on the muscle biopsy specimen. In vitro experiments, including analyses of the mtDNA copy number; levels of ATP, ATPase, and reactive oxygen species (ROS); and the membrane potential, were performed.
Results
The DNA2 heterozygous truncating variant c. 2368C > T (p.Q790X) was identified and verified as the cause of an mtDNA copy number decrement in both functional experiments and muscle tissue analyses. These changes were accompanied by reductions in ATP, ATPase, and ROS levels.
Conclusion
The DNA2 variant was a likely cause of MDS in this patient. These findings expand the mutational spectrum of MDS and improve our understanding of the functions of DNA2 by revealing its novel role in mtDNA maintenance.
Funder
National Natural Science Foundation of China
Beijing Municipal Science and Technology Commission
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献