{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:28:33Z","timestamp":1785796113282,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2015K1A4A3046807"],"award-info":[{"award-number":["NRF-2015K1A4A3046807"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1D1A1B07043216"],"award-info":[{"award-number":["NRF-2018R1D1A1B07043216"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020M3A9E4036527"],"award-info":[{"award-number":["NRF-2020M3A9E4036527"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The intramural grants from the Asan Institute for Life Sciences, AMC","award":["2017-756"],"award-info":[{"award-number":["2017-756"]}]},{"name":"The intramural grants from the Asan Institute for Life Sciences, AMC","award":["2018-756"],"award-info":[{"award-number":["2018-756"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Defects in the mitochondrial genome (mitochondrial DNA (mtDNA)) are associated with both congenital and acquired disorders in humans. Nuclear-encoded DNA polymerase subunit gamma (POLG) plays an important role in mtDNA replication, and proofreading and mutations in POLG have been linked with increased mtDNA deletions. SSBP1 is also a crucial gene for mtDNA replication. Here, we describe a patient diagnosed with Pearson syndrome with large mtDNA deletions that were not detected in the somatic cells of the mother. Exome sequencing was used to evaluate the nuclear factors associated with the patient and his family, which revealed a paternal POLG mutation (c.868C &gt; T) and a maternal SSBP1 mutation (c.320G &gt; A). The patient showed lower POLG and SSBP1 expression than his healthy brothers and the general population of a similar age. Notably, c.868C in the wild-type allele was highly methylated in the patient compared to the same site in both his healthy brothers. These results suggest that the co- deficient expression of POLG and SSBP1 genes could contribute to the development of mtDNA deletion.<\/jats:p>","DOI":"10.3390\/genes12020284","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T21:35:42Z","timestamp":1613597742000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["De Novo Development of mtDNA Deletion Due to Decreased POLG and SSBP1 Expression in Humans"],"prefix":"10.3390","volume":"12","author":[{"given":"Yeonmi","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeho","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongjun","family":"So","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-8654","authenticated-orcid":false,"given":"Mustafa Zafer","family":"Karagozlu","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go Hun","family":"Seo","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2320-6365","authenticated-orcid":false,"given":"Peter C. W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong-Jai","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7240-7868","authenticated-orcid":false,"given":"Eunju","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-2631","authenticated-orcid":false,"given":"Beom Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.beem.2012.05.003","article-title":"Cellular and molecular mechanisms of mitochondrial function","volume":"26","author":"Osellame","year":"2012","journal-title":"Best Pract. 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