{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:49:07Z","timestamp":1785930547312,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Different mitochondrial DNA (mtDNA) mutations have been identified to cause mitochondrial encephalopathy, lactate acidosis and stroke-like episodes (MELAS). The underlying genetic cause leading to an enormous clinical heterogeneity associated with m.3243A&gt;G-related mitochondrial diseases is still poorly understood. Genotype\u2013phenotype correlation (heteroplasmy levels and clinical symptoms) was analysed in 16 patients (15 literature cases and one unreported case) harbouring the m.3243A&gt;G mutation. mtDNA copy numbers were correlated to heteroplasmy levels in 30 different post-mortem tissue samples, including 14 brain samples of a 46-year-old female. In the central nervous system, higher levels of heteroplasmy correlated significantly with lower mtDNA copy numbers. Skeletal muscle levels of heteroplasmy correlated significantly with kidney and liver. There was no significant difference of heteroplasmy levels between clinically affected and unaffected patients. In the patient presented, we found &gt;75% heteroplasmy levels in all central nervous system samples, without harbouring a MELAS phenotype. This underlines previous suggestions, that really high levels in tissues do not automatically lead to a specific phenotype. Missing significant differences of heteroplasmy levels between clinically affected and unaffected patients underline recent suggestions that there are additional factors such as mtDNA copy number and nuclear factors that may also influence disease severity.<\/jats:p>","DOI":"10.3390\/genes11020212","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T08:12:22Z","timestamp":1582618342000},"page":"212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Heteroplasmy and Copy Number in the Common m.3243A&gt;G Mutation\u2014A Post-Mortem Genotype\u2013Phenotype Analysis"],"prefix":"10.3390","volume":"11","author":[{"given":"Leila","family":"Motlagh Scholle","sequence":"first","affiliation":[{"name":"Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Zierz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mawrin","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Otto-von-Guericke University, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Wickenhauser","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Martin-Luther-University Halle-Wittenberg, 06108 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Lehmann Urban","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1101\/gr.250480.119","article-title":"Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution","volume":"29","author":"Tedone","year":"2019","journal-title":"Genome Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/nrg3275","article-title":"Human mitochondrial DNA: Roles of inherited and somatic mutations","volume":"13","author":"Schon","year":"2012","journal-title":"Nat. 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