{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:31:53Z","timestamp":1777516313002,"version":"3.51.4"},"reference-count":16,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Child Neurology Open"],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>In the field of mitochondrial medicine, correlation of clinical phenotype with mutation heteroplasmy remains an outstanding question with few, if any, clear thresholds corresponding to a given phenotype. The m.8344A&gt;G mutation is most commonly associated with myoclonus epilepsy and ragged red fiber syndrome (MERRF) at varying levels of heteroplasmy. However, a handful of cases been previously reported in which individuals homoplasmic or nearly homoplasmic for this mutation in the blood have presented with multiple bulbar palsies, respiratory failure, and progressive neurologic decline almost uniformly following a respiratory illness. MRI brain in all affected individuals revealed symmetric T2 hyperintense lesions of subcortical gray matter structures, consistent with Leigh syndrome. Here, we present 3 cases with clinical, biochemical, and neuro-imaging findings with the additional reporting of spinal lesions. This new phenotype supports a heteroplasmy-dependent phenotype model for this mutation and recognition of this can help clinicians with diagnosis and anticipatory clinical guidance.<\/jats:p>","DOI":"10.1177\/2329048x21991382","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T04:44:05Z","timestamp":1614660245000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Leigh Syndrome as a Phenotype of Near-Homoplasmic m.8344 A&gt;G Variant in Children"],"prefix":"10.1177","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5045-9301","authenticated-orcid":false,"given":"Sam Nicholas","family":"Russo","sequence":"first","affiliation":[{"name":"Division of Child and Adolescent Neurology, Department of Pediatrics, The University of Texas McGovern Medical School, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Mitochondrial Medicine Frontier Program, Division of Human Genetics, Children\u2019s Hospital of Philadelphia, PA, USA"},{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amel","family":"Karaa","sequence":"additional","affiliation":[{"name":"Mitochondrial Disease Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Kay","family":"Koenig","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Neurology, Department of Pediatrics, The University of Texas McGovern Medical School, Houston, TX, USA"},{"name":"The University of Texas Mitochondrial Center of Excellence, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"bibr1-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R117.809194"},{"key":"bibr2-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708262"},{"key":"bibr3-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9465-2"},{"key":"bibr4-2329048X21991382","unstructured":"DiMauro S, MERRF HM. GeneReviews\n                      \u00ae [Internet]\n                      . Published 2003. Updated 2015. Accessed June 1, 2020. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1520\/"},{"key":"bibr5-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24551"},{"key":"bibr6-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390311"},{"key":"bibr7-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-52"},{"key":"bibr8-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.2.264"},{"issue":"4","key":"bibr9-2329048X21991382","first-page":"852","volume":"50","author":"Tatuch Y","year":"1992","journal-title":"Am J Hum Gen"},{"key":"bibr10-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1177\/08830738060210010901"},{"key":"bibr11-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.1.219"},{"key":"bibr12-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0865"},{"key":"bibr13-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.08.006"},{"key":"bibr14-2329048X21991382","first-page":"9","author":"Shen C","year":"2018","journal-title":"Front Neurol"},{"key":"bibr15-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.6.1200"},{"key":"bibr16-2329048X21991382","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90157-0"}],"container-title":["Child Neurology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2329048X21991382","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/2329048X21991382","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2329048X21991382","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:58:13Z","timestamp":1777391893000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/2329048X21991382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":16,"alternative-id":["10.1177\/2329048X21991382"],"URL":"https:\/\/doi.org\/10.1177\/2329048x21991382","relation":{},"ISSN":["2329-048X","2329-048X"],"issn-type":[{"value":"2329-048X","type":"print"},{"value":"2329-048X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,1]]},"article-number":"2329048X21991382"}}