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Of the ~\u2009170 known RNA chemical modifications, methylation is among the most common. Loss of function mutations in<jats:italic>NSUN3<\/jats:italic>, encoding the 5-methylcytosine (m5C) methyltransferase NSun3, have been linked to multisystem mitochondrial disease associated with combined oxidative phosphorylation deficiency. Here, we report a patient with early-onset mitochondrial encephalomyopathy and seizures in whom the novel biallelic<jats:italic>NSUN3<\/jats:italic>missense variants c.421G&gt;C (p.A141P) and c.454T&gt;A (p.C152S) were detected. Segregation studies and in silico functional analysis confirmed the likely pathogenic effects of both variants. These findings expand the molecular and phenotypic spectrum of<jats:italic>NSUN3<\/jats:italic>-related mitochondrial disease.<\/jats:p>","DOI":"10.1007\/s12031-020-01595-8","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T16:06:59Z","timestamp":1591114019000},"page":"1962-1965","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures"],"prefix":"10.1007","volume":"70","author":[{"given":"Arumugam","family":"Paramasivam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angamuthu K.","family":"Meena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Challa","family":"Venkatapathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6123-4551","authenticated-orcid":false,"given":"Robert D.S.","family":"Pitceathly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-0106","authenticated-orcid":false,"given":"Kumarasamy","family":"Thangaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"1595_CR1","doi-asserted-by":"publisher","first-page":"D303","DOI":"10.1093\/nar\/gkx1030","volume":"46","author":"P Boccaletto","year":"2018","unstructured":"Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B, Wirecki TK, de Crecy-Lagard V, Ross R, Limbach PA, Kotter A et al (2018) MODOMICS: a database of RNA modification pathways. 2017 update. 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The study was approved by the Institutional Ethical Committee (IEC) of CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India, and Nizam\u2019s Institute of Medical Sciences (NIMS), Hyderabad, India.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}