ArticlePloS one2017
Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- African swine fever virus MGF505-3R facilitates ferroptosis to restrict TBK1-IRF3 pathway.Microbiology spectrum · 2025Article
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 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
- Bi-allelic KARS1 pathogenic variants affecting functions of cytosolic and mitochondrial isoforms are associated with a progressive and multisystem disease.Human mutation · 2021Article
- Mitochondrial Aminoacyl-tRNA Synthetase and Disease: The Yeast Contribution for Functional Analysis of Novel Variants.International journal of molecular sciences · 2021Review
- AAV1.NT-3 gene therapy in a CMT2D model: phenotypic improvements inBrain communications · 2021Article
- Compound Heterozygous Variants in Pediatric Cancers: A Systematic Review.Frontiers in genetics · 2020Review
- Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases.The Journal of biological chemistry · 2019Review
- Aminoacyl-tRNA synthetase deficiencies in search of common themes.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Clinical Application of Genome and Exome Sequencing as a Diagnostic Tool for Pediatric Patients: a Scoping Review of the Literature.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease.Current opinion in pediatrics · 2018Review
- Mitochondrial DNA transcription and translation: clinical syndromes.Essays in biochemistry · 2018Review
- A Novel Mutation ofFrontiers in neurology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycyl-tRNA synthetase (GARS; OMIM 600287) is one of thirty-seven tRNA-synthetase genes that catalyses the synthesis of glycyl-tRNA, which is required to insert glycine into proteins within the cytosol and mitochondria. To date, eighteen mutations in GARS have been reported in patients with autosomal-dominant Charcot-Marie-Tooth disease type 2D (CMT2D; OMIM 601472), and/or distal spinal muscular atrophy type V (dSMA-V; OMIM 600794). In this study, we report a patient with clinical and biochemical features suggestive of a mitochondrial respiratory chain (MRC) disorder including mild left ventricular posterior wall hypertrophy, exercise intolerance, and lactic acidosis. Using whole exome sequencing we identified compound heterozygous novel variants, c.803C>T; p.(Thr268Ile) and c.1234C>T; p.(Arg412Cys), in GARS in the proband. Spectrophotometric evaluation of the MRC complexes showed reduced activity of Complex I, III and IV in patient skeletal muscle and reduced Complex I and IV activity in the patient liver, with Complex IV being the most severely affected in both tissues. Immunoblot analysis of GARS protein and subunits of the MRC enzyme complexes in patient fibroblast extracts showed significant reduction in GARS protein levels and Complex IV. Together these studies provide evidence that the identified compound heterozygous GARS variants may be the cause of the mitochondrial dysfunction in our patient.
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