ArticleAmerican journal of human genetics2018
Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Monoallelic POLR3A Variants Cause Early-Onset Peripheral Neuropathy.Annals of neurology · 2026Article
- EIF2AK2-related hypomyelinating leukoencephalopathy presenting with congenital bilateral vocal cord paralysis and a spinal cord lesion.Neurogenetics · 2026Article
- Compound heterozygosity of a novel missense variant and exonic deletion in hypomyelinating leukodystrophy 15.Neurogenetics · 2026Article
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Regulation of Protein Synthesis at the Translational Level: Novel Findings in Cardiovascular Biology.Biomolecules · 2025Review
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Setting the Stage for Treatment of Aminoacyl-tRNA Synthetase (ARS)1-Deficiencies: Phenotypic Characterization and a Review of Treatment Effects.Journal of inherited metabolic disease · 2025Review
- Extracellular vesicle signatures from eye lavage as novel non-invasive biomarkers for hypoxic ischaemic insult-findings from a neonatal mouse model.Frontiers in medical technology · 2025Article
- GART promotes the proliferation and migration of human non-small cell lung cancer cell lines A549 and H1299 by targeting PAICS-Akt-β-catenin pathway.Frontiers in oncology · 2025Article
- Aminoacyl-tRNA synthetase defects in neurological diseases.IUBMB life · 2025Review
- Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.Nucleic acids research · 2024Article
- AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Towards a Treatment for Leukodystrophy Using Cell-Based Interception and Precision Medicine.Biomolecules · 2024Review
- Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA mNature communications · 2024Article
- AGenes · 2024Article
- The 37TrillionCells initiative for improving global healthcare via cell-based interception and precision medicine: focus on neurodegenerative diseases.Molecular brain · 2024Review
- Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.Scientific reports · 2024Article
- Article
- Phosphocode-dependent glutamyl-prolyl-tRNA synthetase 1 signaling in immunity, metabolism, and disease.Experimental & molecular medicine · 2023Review
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Authors and funding
21 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypomyelinating leukodystrophies are genetic disorders characterized by insufficient myelin deposition during development. They are diagnosed on the basis of both clinical and MRI features followed by genetic confirmation. Here, we report on four unrelated affected individuals with hypomyelination and bi-allelic pathogenic variants in EPRS, the gene encoding cytoplasmic glutamyl-prolyl-aminoacyl-tRNA synthetase. EPRS is a bifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. It is a subunit of a large multisynthetase complex composed of eight aminoacyl-tRNA synthetases and its three interacting proteins. In total, five different EPRS mutations were identified. The p.Pro1115Arg variation did not affect the assembly of the multisynthetase complex (MSC) as monitored by affinity purification-mass spectrometry. However, immunoblot analyses on protein extracts from fibroblasts of the two affected individuals sharing the p.Pro1115Arg variant showed reduced EPRS amounts. EPRS activity was reduced in one affected individual's lymphoblasts and in a purified recombinant protein model. Interestingly, two other cytoplasmic aminoacyl-tRNA synthetases have previously been implicated in hypomyelinating leukodystrophies bearing clinical and radiological similarities to those in the individuals we studied. We therefore hypothesized that leukodystrophies caused by mutations in genes encoding cytoplasmic aminoacyl-tRNA synthetases share a common underlying mechanism, such as reduced protein availability, abnormal assembly of the multisynthetase complex, and/or abnormal aminoacylation, all resulting in reduced translation capacity and insufficient myelin deposition in the developing brain.
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