ArticleAnnals of clinical and translational neurology2020
RARS1-related hypomyelinating leukodystrophy: Expanding the spectrum.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 29 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Aminoacyl-tRNA Synthetases: Variant Classification, Functional Assays, and Emerging Therapeutic Strategies.Journal of inherited metabolic disease · 2026Review
- A disease-causing isoleucyl-tRNA synthetase variant leads to altered protein complex formation and cellular stress response.The Journal of biological chemistry · 2026Article
- Overview of genetic variants in a cohort of Iranian patients with leukodystrophy.Scientific reports · 2025Article
- 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
- Overview of Neuro-Ophthalmic Findings in Leukodystrophies.Journal of clinical medicine · 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
- RARS1-related developmental and epileptic encephalopathy.Epilepsia open · 2023Review
- Expression and Activity of the Transcription Factor CCAAT/Enhancer-Binding Protein β (C/EBPβ) Is Regulated by Specific Pulse-Modulated Radio Frequencies in Oligodendroglial Cells.International journal of molecular sciences · 2023Article
- Mutation in PYCR2 gene and hypomyelinating leukodystrophy in children: a case report study.Annals of medicine and surgery (2012) · 2023Article
- Aminoacyl-tRNA Synthetases: On Anti-Synthetase Syndrome and Beyond.Frontiers in immunology · 2022Review
- Emerging cellular themes in leukodystrophies.Frontiers in cell and developmental biology · 2022Review
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Biallelic PI4KA variants cause neurological, intestinal and immunological disease.Brain : a journal of neurology · 2021Article
- Expanded phenotype of AARS1-related white matter disease.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease.Science China. Life sciences · 2021Article
- Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Regulation of ex-translational activities is the primary function of the multi-tRNA synthetase complex.Nucleic acids research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 18 institutions in 7 countries.
Funding
Abstract
objectiveBiallelic variants in RARS1, encoding the cytoplasmic tRNA synthetase for arginine (ArgRS), cause a hypomyelinating leukodystrophy. This study aimed to investigate clinical, neuroradiological and genetic features of patients with RARS1-related disease, and to identify possible genotype-phenotype relationships.
methodsWe performed a multinational cross-sectional survey among 20 patients with biallelic RARS1 variants identified by next-generation sequencing techniques. Clinical data, brain MRI findings and genetic results were analyzed. Additionally, ArgRS activity was measured in fibroblasts of four patients, and translation of long and short ArgRS isoforms was quantified by western blot.
resultsClinical presentation ranged from severe (onset in the first 3 months, usually with refractory epilepsy and early brain atrophy), to intermediate (onset in the first year with nystagmus and spasticity), and mild (onset around or after 12 months with minimal cognitive impairment and preserved independent walking). The most frequent RARS1 variant, c.5A>G, led to mild or intermediate phenotypes, whereas truncating variants and variants affecting amino acids close to the ArgRS active centre led to severe phenotypes. ArgRS activity was significantly reduced in three patients with intermediate and severe phenotypes; in a fourth patient with intermediate to severe presentation, we measured normal ArgRS activity, but found translation mainly of the short instead of the long ArgRS isoform.
interpretationVariants in RARS1 impair ArgRS activity and do not only lead to a classic hypomyelination presentation with nystagmus and spasticity, but to a wide spectrum, ranging from severe, early-onset epileptic encephalopathy with brain atrophy to mild disease with relatively preserved myelination.
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.