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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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The <jats:italic>DNA2<\/jats:italic> heterozygous truncating variant c. 2368C\u2009&gt;\u2009T (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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The <jats:italic>DNA2<\/jats:italic> 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 <jats:italic>DNA2<\/jats:italic> by revealing its novel role in mtDNA maintenance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s10038-022-01075-4","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T07:06:08Z","timestamp":1662361568000},"page":"691-699","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["DNA2 mutation causing multisystemic disorder with impaired mitochondrial DNA maintenance"],"prefix":"10.1038","volume":"67","author":[{"given":"Jiayu","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1206-1778","authenticated-orcid":false,"given":"Jianwen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhe","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"1075_CR1","doi-asserted-by":"publisher","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","volume":"2","author":"GS Gorman","year":"2016","unstructured":"Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, et al. 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