Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures

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) methylt...

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Autores principales: Paramasivam, Arumugam, Meena, Angamuthu K., Venkatapathi, Challa, Pitceathly, Robert D.S., Thangaraj, Kumarasamy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658056/
https://www.ncbi.nlm.nih.gov/pubmed/32488845
http://dx.doi.org/10.1007/s12031-020-01595-8
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author Paramasivam, Arumugam
Meena, Angamuthu K.
Venkatapathi, Challa
Pitceathly, Robert D.S.
Thangaraj, Kumarasamy
author_facet Paramasivam, Arumugam
Meena, Angamuthu K.
Venkatapathi, Challa
Pitceathly, Robert D.S.
Thangaraj, Kumarasamy
author_sort Paramasivam, Arumugam
collection PubMed
description 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.
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spelling pubmed-76580562020-11-12 Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures Paramasivam, Arumugam Meena, Angamuthu K. Venkatapathi, Challa Pitceathly, Robert D.S. Thangaraj, Kumarasamy J Mol Neurosci Article 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. Springer US 2020-06-02 2020 /pmc/articles/PMC7658056/ /pubmed/32488845 http://dx.doi.org/10.1007/s12031-020-01595-8 Text en © The Author(s) 2020, corrected publication July 2020 Open Access 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/.
spellingShingle Article
Paramasivam, Arumugam
Meena, Angamuthu K.
Venkatapathi, Challa
Pitceathly, Robert D.S.
Thangaraj, Kumarasamy
Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures
title Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures
title_full Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures
title_fullStr Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures
title_full_unstemmed Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures
title_short Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures
title_sort novel biallelic nsun3 variants cause early-onset mitochondrial encephalomyopathy and seizures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658056/
https://www.ncbi.nlm.nih.gov/pubmed/32488845
http://dx.doi.org/10.1007/s12031-020-01595-8
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