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Heteroplasmy differed markedly among blood, skeletal muscle, and myocardium, indicating that blood may not represent variant loads in energy\u2010demanding tissues. Reported values generally reflected the lowest observed levels in affected individuals or family\u2010specific boundaries rather than validated pathogenic cutoffs. Functional findings support a staged mechanism involving disturbed transfer RNA processing, structure, stability, or aminoacylation, followed by impaired mitochondrial protein synthesis and respiratory\u2010chain dysfunction. Integrated mechanistic support was limited to a few variants, including m.4295A&gt;G; evidence for most variants remained incomplete or indirect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Diagnosis requires tissue\u2010informed heteroplasmy assessment integrated with phenotype, maternal family history, and functional evidence. Current treatment is supportive, and proposed reproductive and molecular strategies lack\n                      <jats:italic>MT\u2010TI<\/jats:italic>\n                      \u2010specific clinical\u2010trial evidence.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70056","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:37:06Z","timestamp":1788147426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding the Genetic and Phenotypic Spectrum of\n                    <i>MT\u2010TI<\/i>\n                    Mitochondrial Diseases"],"prefix":"10.1111","author":[{"given":"Enchi","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract the First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei China"},{"name":"Second School of Clinical Medicine Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract the First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract the First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enze","family":"Chen","sequence":"additional","affiliation":[{"name":"First School of Clinical Medicine Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qidi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Second School of Clinical Medicine Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract the First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.02.173"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/290457a0"},{"key":"e_1_2_14_4_1","unstructured":"Arany E. 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