ArticleHuman mutation2018
Clinical, biochemical, and genetic features associated with VARS2-related mitochondrial disease.
Article in Human mutation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 27 citations in OpenAlex.
- Tailored Amino Acid Treatment for Pediatric Patients With Mitochondrial Aminoacyl-tRNA Synthetase Deficiencies.Journal of inherited metabolic disease · 2026Article
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- Article
- Multi-omics Mendelian randomization analysis identifies SPATA20 as a cross-omic target in primary open angle glaucoma.International journal of ophthalmology · 2026Article
- Novel Variants in VARS2 Demonstrate the Phenotypic Variability of a Rare Mitochondriopathy That Responds to Valine Supplementation.Journal of inherited metabolic disease · 2025Article
- Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis.Molecular neurobiology · 2023Review
- Article
- VARS2 Depletion Leads to Activation of the Integrated Stress Response and Disruptions in Mitochondrial Fatty Acid Oxidation.International journal of molecular sciences · 2022Article
- Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center.Frontiers in genetics · 2022Article
- The regulatory roles of aminoacyl-tRNA synthetase in cardiovascular disease.Molecular therapy. Nucleic acids · 2021Review
- Case Report and Review of the Literature: A New and a Recurrent Variant in theFrontiers in pediatrics · 2021Article
- A Mitochondrial tRNA Mutation Causes Axonal CMT in a Large Venezuelan Family.Annals of neurology · 2020Article
- A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2019Article
- A novel VARS2 gene variant in a patient with epileptic encephalopathy.Upsala journal of medical sciences · 2019Article
- The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies.Acta ophthalmologica · 2019Article
- VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype.BMC medical genetics · 2019Article
- When a common biological role does not imply common disease outcomes: Disparate pathology linked to human mitochondrial aminoacyl-tRNA synthetases.The Journal of biological chemistry · 2019Review
- The nuclear background influences the penetrance of the near-homoplasmic m.1630 A > G MELAS variant in a symptomatic proband and asymptomatic mother.Molecular genetics and metabolism · 2019Article
- Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study.Frontiers in pediatrics · 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
22 authors at 12 institutions in 8 countries.
Funding
Abstract
In recent years, an increasing number of mitochondrial disorders have been associated with mutations in mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs), which are key enzymes of mitochondrial protein synthesis. Bi-allelic functional variants in VARS2, encoding the mitochondrial valyl tRNA-synthetase, were first reported in a patient with psychomotor delay and epilepsia partialis continua associated with an oxidative phosphorylation (OXPHOS) Complex I defect, before being described in a patient with a neonatal form of encephalocardiomyopathy. Here we provide a detailed genetic, clinical, and biochemical description of 13 patients, from nine unrelated families, harboring VARS2 mutations. All patients except one, who manifested with a less severe disease course, presented at birth exhibiting severe encephalomyopathy and cardiomyopathy. Features included hypotonia, psychomotor delay, seizures, feeding difficulty, abnormal cranial MRI, and elevated lactate. The biochemical phenotype comprised a combined Complex I and Complex IV OXPHOS defect in muscle, with patient fibroblasts displaying normal OXPHOS activity. Homology modeling supported the pathogenicity of VARS2 missense variants. The detailed description of this cohort further delineates our understanding of the clinical presentation associated with pathogenic VARS2 variants and we recommend that this gene should be considered in early-onset mitochondrial encephalomyopathies or encephalocardiomyopathies.
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.