{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:51:02Z","timestamp":1762059062217,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009553","name":"Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["AZV 17-30965A"],"award-info":[{"award-number":["AZV 17-30965A"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>In this study, we report on a novel heteroplasmic pathogenic variant in mitochondrial DNA (mtDNA). The studied patient had myoclonus, epilepsy, muscle weakness, and hearing impairment and harbored a heteroplasmic m.8315A&gt;C variant in the MTTK gene with a mutation load ranging from 71% to &gt;96% in tested tissues. In muscle mitochondria, markedly decreased activities of respiratory chain complex I + III and complex IV were observed together with mildly reduced amounts of complex I and complex V (with the detection of V*- and free F1-subcomplexes) and a diminished level of complex IV holoenzyme. This pattern was previously seen in other MTTK pathogenic variants. The novel variant was not present in internal and publicly available control databases. Our report further expands the spectrum of MTTK variants associated with mitochondrial encephalopathies in adults.<\/jats:p>","DOI":"10.3390\/genes13071245","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:17:10Z","timestamp":1657844230000},"page":"1245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel MTTK Gene Variant m.8315A&gt;C as a Cause of MERRF Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0084-7730","authenticated-orcid":false,"given":"Hana","family":"\u0160tufkov\u00e1","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Kol\u00e1\u0159ov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate\u0159ina","family":"Lokvencov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1\u0161","family":"Honz\u00edk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-7919","authenticated-orcid":false,"given":"Ji\u0159\u00ed","family":"Zeman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-225X","authenticated-orcid":false,"given":"Hana","family":"Hans\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark\u00e9ta","family":"Tesa\u0159ov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/0092-8674(90)90059-N","article-title":"Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation","volume":"61","author":"Shoffner","year":"1990","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/1873-3468.14049","article-title":"The molecular pathology of pathogenic mitochondrial tRNA variants","volume":"595","author":"Richter","year":"2021","journal-title":"FEBS Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrneurol.2013.126","article-title":"The clinical maze of mitochondrial neurology","volume":"9","author":"DiMauro","year":"2013","journal-title":"Nat. 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