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

• Published in: Journal of molecular neuroscience Vol. 70; no. 12; pp. 1962 - 1965
• Main Authors: Paramasivam, Arumugam, Meena, Angamuthu K., Venkatapathi, Challa, Pitceathly, Robert D.S., Thangaraj, Kumarasamy
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2020; Springer Nature B.V
• Subjects: Age; Biomedical and Life Sciences; Biomedicine; Brain - diagnostic imaging; Cell Biology; Convulsions & seizures; DNA methylation; Female; Functional analysis; Gene expression; Humans; Male; Methyltransferase; Methyltransferases - genetics; Mitochondria; Mitochondrial Encephalomyopathies - genetics; Mitochondrial Encephalomyopathies - pathology; Mutation; Mutation, Missense; Neurochemistry; Neurology; Neurosciences; Oxidative phosphorylation; Pedigree; Phenotype; Phosphorylation; Post-transcription; Proteomics; Ribonucleic acid; RNA; Seizures; Seizures - genetics; Seizures - pathology; Encephalomyopathy; Mitochondrial disorders; Epitranscriptomics; mtDNA; Seizures; NSUN3
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-020-01595-8

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.