{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T21:25:44Z","timestamp":1787952344596,"version":"build-2784847793"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial disorders can present with a wide range of clinical and biochemical phenotypes. Mitochondrial DNA variants may be influenced by factors such as degree of heteroplasmy and tissue distribution. We present a four\u2010generation family in which 10 individuals carry a pathogenic mitochondrial variant (m.5537_5538insT, <jats:italic>MT\u2010TW<\/jats:italic> gene) with differing levels of heteroplasmy and clinical features. This genetic variant has been documented in two prior reports, both in individuals with Leigh syndrome. In the current family, three individuals have severe mitochondrial symptoms including Leigh syndrome (patient 1, 100% in blood), MELAS (patient 2, 97% heteroplasmy in muscle), and MELAS\u2010like syndrome (patient 3, 50% heteroplasmy in blood and 100% in urine). Two individuals have mild mitochondrial symptoms (patient 4, 50% in blood and 67% in urine and patient 5, 50% heteroplasmy in blood and 30% in urine). We observe that this variant is associated with multiple mitochondrial presentations and phenotypes, including MELAS syndrome for which this variant has not previously been reported. We also demonstrate that the level of heteroplasmy of the mitochondrial DNA variant correlates with the severity of clinical presentation; however, not with the specific mitochondrial syndrome.<\/jats:p>","DOI":"10.1002\/ajmg.a.63378","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T06:43:19Z","timestamp":1693550599000},"page":"2890-2897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The mitochondrial tRNA MT\u2010TW m.5537_5538insT variant presents with significant intra\u2010familial clinical variability"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-2556","authenticated-orcid":false,"given":"Lauren","family":"Strasser","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Doja","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"},{"name":"Department of Pediatrics University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Davila","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"},{"name":"Department of Radiology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-0821","authenticated-orcid":false,"given":"Pranesh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Ottawa  Ottawa Ontario Canada"},{"name":"Division of Metabolics and Newborn Screening Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-6201","authenticated-orcid":false,"given":"Danielle K.","family":"Bourque","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Ottawa  Ottawa Ontario Canada"},{"name":"Division of Metabolics and Newborn Screening Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304426"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.693734"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000018634"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2014.03.009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e328306ebb6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022567"},{"key":"e_1_2_9_8_1","volume-title":"GeneReviews: MELAS","author":"El\u2010Hattab A. 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