ArticleAmerican journal of human genetics2010
Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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126 citing papers in PubMed, 234 citations in OpenAlex.
- Generation of a Patient-Derived Inducible Pluripotent Stem Cell Model for Studying theInternational journal of stem cells · 2026Article
- Congenital-onset MLASA2 from a novelJournal of neuromuscular diseases · 2026Review
- Interplay of anemia in inborn errors of energy metabolism.Scientific reports · 2026Observational
- Respiratory complex I deficiency caused by a novel multi-exonic PUS1 deletion.Journal of human genetics · 2026Article
- A systematic analysis of mitochondrial aminoacyl tRNA synthetase variants in a rare disease cohort.European journal of human genetics : EJHG · 2026Article
- Correlation of MLASA2 Clinical Phenotype and Survival with Mt-TyrRS Protein Damage: Linking Systematic Review, Meta-Analysis and 3D Hotspot Mapping.Current issues in molecular biology · 2026Review
- First Latin American Case of MLASA2 Caused by a Pathogenic Variant in the Anticodon-Binding Domain ofInternational journal of molecular sciences · 2025Article
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- The role of genetic testing in accurate diagnosis of X-linked sideroblastic anemia: novel ALAS2 mutations and the impact of X-chromosome inactivation.Scientific reports · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Amino acid supplementation in mitochondrial aminoacyl-tRNA synthetase defects: two case reports of tyrosine supplementation inFrontiers in pediatrics · 2025Article
- A kinetic model for compound heterozygous pathogenic variants in Tyrosyl-tRNA synthetase gene YARS2-Associated neonatal phenotype.The Journal of biological chemistry · 2025Article
- Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.Nucleic acids research · 2024Article
- Identification of the DNA methylation signature of Mowat-Wilson syndrome.European journal of human genetics : EJHG · 2024Article
- Clinical and genetic analysis of essential hypertension with mitochondrial tRNAZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Article
- Pseudouridine synthase 1 regulates erythropoiesis via transfer RNAs pseudouridylation and cytoplasmic translation.iScience · 2024Article
- Mitochondrial myopathies diagnosed in adulthood: clinico-genetic spectrum and long-term outcomes.Brain communications · 2024Article
- A clinical approach to diagnosis and management of mitochondrial myopathies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Clinical drivers of hospitalisation in patients with mitochondrial diseases.BMJ neurology open · 2024Article
- Severe neonatal onset neuroregression with paroxysmal dystonia and apnoea: Expanding the phenotypic and genotypic spectrum ofJIMD reports · 2023Article
66 more citing papers are in PubMed but not listed here.
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12 authors at 8 institutions in 2 countries.
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Abstract
Mitochondrial respiratory chain disorders are a heterogeneous group of disorders in which the underlying genetic defect is often unknown. We have identified a pathogenic mutation (c.156C>G [p.F52L]) in YARS2, located at chromosome 12p11.21, by using genome-wide SNP-based homozygosity analysis of a family with affected members displaying myopathy, lactic acidosis, and sideroblastic anemia (MLASA). We subsequently identified the same mutation in another unrelated MLASA patient. The YARS2 gene product, mitochondrial tyrosyl-tRNA synthetase (YARS2), was present at lower levels in skeletal muscle whereas fibroblasts were relatively normal. Complex I, III, and IV were dysfunctional as indicated by enzyme analysis, immunoblotting, and immunohistochemistry. A mitochondrial protein-synthesis assay showed reduced levels of respiratory chain subunits in myotubes generated from patient cell lines. A tRNA aminoacylation assay revealed that mutant YARS2 was still active; however, enzyme kinetics were abnormal compared to the wild-type protein. We propose that the reduced aminoacylation activity of mutant YARS2 enzyme leads to decreased mitochondrial protein synthesis, resulting in mitochondrial respiratory chain dysfunction. MLASA has previously been associated with PUS1 mutations; hence, the YARS2 mutation reported here is an alternative cause of MLASA.
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