Paramasivam, A;
Meena, AK;
Venkatapathi, C;
Pitceathly, RDS;
Thangaraj, K;
(2020)
Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures.
Journal of Molecular Neuroscience
10.1007/s12031-020-01595-8.
(In press).
Preview |
Text
Paramasivam2020_Article_NovelBiallelicNSUN3VariantsCau(1).pdf - Published Version Download (1MB) | Preview |
Abstract
Epitranscriptomic systems enable post-transcriptional modifications of cellular RNA that are essential for regulating gene expression. Of the ~ 170 known RNA chemical modifications, methylation is among the most common. Loss of function mutations in NSUN3, 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 NSUN3 missense variants c.421G>C (p.A141P) and c.454T>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 NSUN3-related mitochondrial disease.
| Type: | Article |
|---|---|
| Title: | Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s12031-020-01595-8 |
| Publisher version: | https://doi.org/10.1007/s12031-020-01595-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Epitranscriptomics, Mitochondrial disorders, mtDNA, NSUN3, Encephalomyopathy, Seizures |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10105386 |
Archive Staff Only
 |
View Item |
