ArticleEuropean journal of human genetics : EJHG2017
Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease.
Article in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- A near-complete map of human cytosolic degrons and their relevance for disease.Science advances · 2026Article
- 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
- Uncovering potential causal genes for undiagnosed congenital anomalies using an in-house pipeline for trio-based whole-genome sequencing.Human genomics · 2025Article
- A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.Neuroscience bulletin · 2024Article
- A loss of function mutation in CLDN25 causing Pelizaeus-Merzbacher-like leukodystrophy.Human molecular genetics · 2024Article
- Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA mNature communications · 2024Article
- RARS1-related hypomyelinating leukodystrophy-9 (HLD-9) in two distinct Iranian families: Case report and literature review.Molecular genetics & genomic medicine · 2024Review
- Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.Current topics in medicinal chemistry · 2024Review
- Molecular Pathogenic Mechanisms of Hypomyelinating Leukodystrophies (HLDs).Neurology international · 2023Review
- RARS1-related developmental and epileptic encephalopathy.Epilepsia open · 2023Review
- Mechanisms of Diseases Associated with Mutation in GJC2/Connexin 47.Biomolecules · 2023Review
- RNA Polymerases I and III in development and disease.Seminars in cell & developmental biology · 2023Review
- Four pedigrees with aminoacyl-tRNA synthetase abnormalities.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease.Science China. Life sciences · 2021Article
- Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report.International journal of general medicine · 2021Article
- Comparative Transcriptomics and RNA-Seq-Based Bulked Segregant Analysis Reveals Genomic Basis UnderlyingFrontiers in microbiology · 2021Article
- 3-Dimensional architecture of the human multi-tRNA synthetase complex.Nucleic acids research · 2020Article
- RARS1-related hypomyelinating leukodystrophy: Expanding the spectrum.Annals of clinical and translational neurology · 2020Article
- Hypomyelinating leukodystrophy-associated mutation of RARS leads it to the lysosome, inhibiting oligodendroglial morphological differentiation.Biochemistry and biophysics reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pelizaeus-Merzbacher disease (PMD) is a rare Mendelian disorder characterised by central nervous system hypomyelination. PMD typically manifests in infancy or early childhood and is caused by mutations in proteolipid protein-1 (PLP1). However, variants in several other genes including gap junction protein gamma 2 (GJC2) can also cause a similar phenotype and are referred to PMD-like disease (PMLD). Whole-exome sequencing in two siblings presenting with clinical symptoms of PMD revealed a homozygous variant in the arginyl-tRNA synthetase (RARS) gene: NM_002887.3: c.[5A>G] p.(Asp2Gly). Subsequent screening of a PMD cohort without a genetic diagnosis identified an unrelated individual with novel compound heterozygous variants including a missense variant c.[1367C>T] p.(Ser456Leu) and a de novo deletion c.[1846_1847delTA] p.(Tyr616Leufs*6). Protein levels of RARS and the multi-tRNA synthetase complex into which it assembles were found to be significantly reduced by 80 and 90% by western blotting and Blue native-PAGE respectively using patient fibroblast extracts. As RARS is involved in protein synthesis whereby it attaches arginine to its cognate tRNA, patient cells were studied to determine their ability to proliferate with limiting amounts of this essential amino acid. Patient fibroblasts cultured in medium with limited arginine at 30 °C and 40 °C, showed a significant decrease in fibroblast proliferation (P<0.001) compared to control cells, suggestive of inefficiency of protein synthesis in the patient cells. Our functional studies provide further evidence that RARS is a PMD-causing gene.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.