ArticleJIMD reports2016
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.
Article in JIMD reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- The landscape of genetic variations in non-syndromic primary ovarian insufficiency in the MENA region: a systematic review.Frontiers in endocrinology · 2023Pooled it
- tRNA-derived small noncoding RNAs: Roles in brain aging and neurodegenerative disorders.Zoological research · 2025Review
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- Comprehensive review of mitochondrial nephropathy-a renal phenotype in mitochondrial disease: causative genes, clinical and pathological features, diagnosis, prognosis, and treatment.Clinical and experimental nephrology · 2025Review
- LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss.European journal of human genetics : EJHG · 2023Article
- The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease.Genes · 2022Review
- New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder.Human genetics · 2022Review
- Aminoacyl-tRNA synthetases in human health and disease.Frontiers in physiology · 2022Review
- Biallelic mutations in theHaematologica · 2021Article
- Lethal variants in humans: lessons learned from a large molecular autopsy cohort.Genome medicine · 2021Article
- Two Novel Variants inJournal of clinical medicine · 2021Article
- BiallelicHaematologica · 2021Article
- Single-Cell Transcriptional Profiling Reveals Sex and Age Diversity of Gene Expression in Mouse Endothelial Cells.Frontiers in genetics · 2021Article
- Perrault syndrome: Clinical report and retrospective analysis.Molecular genetics & genomic medicine · 2020Article
- Article
- LARS2-Perrault syndrome: a new case report and literature review.BMC medical genetics · 2020Review
- tRNA Metabolism and Neurodevelopmental Disorders.Annual review of genomics and human genetics · 2019Review
- Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders.Journal of translational medicine · 2019Article
- Mutations in the mitochondrial tryptophanyl-tRNA synthetase cause growth retardation and progressive leukoencephalopathy.Molecular genetics & genomic medicine · 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
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
Pathogenic variants in mitochondrial aminoacyl-tRNA synthetases result in a broad range of mitochondrial respiratory chain disorders despite their shared role in mitochondrial protein synthesis. LARS2 encodes the mitochondrial leucyl-tRNA synthetase, which attaches leucine to its cognate tRNA. Sequence variants in LARS2 have previously been associated with Perrault syndrome, characterized by premature ovarian failure and hearing loss (OMIM #615300). In this study, we report variants in LARS2 that are associated with a severe multisystem metabolic disorder. The proband was born prematurely with severe lactic acidosis, hydrops, and sideroblastic anemia. She had multisystem complications with hyaline membrane disease, impaired cardiac function, a coagulopathy, pulmonary hypertension, and progressive renal disease and succumbed at 5 days of age. Whole exome sequencing of patient DNA revealed compound heterozygous variants in LARS2 (c.1289C>T; p.Ala430Val and c.1565C>A; p.Thr522Asn). The c.1565C>A (p.Thr522Asn) LARS2 variant has previously been associated with Perrault syndrome and both identified variants are predicted to be damaging (SIFT, PolyPhen). Muscle and liver samples from the proband did not display marked mitochondrial respiratory chain enzyme deficiency. Immunoblotting of patient muscle and liver showed LARS2 levels were reduced in liver and complex I protein levels were reduced in patient muscle and liver. Aminoacylation assays revealed p.Ala430Val LARS2 had an 18-fold loss of catalytic efficiency and p.Thr522Asn a 9-fold loss compared to wild-type LARS2. We suggest that the identified LARS2 variants are responsible for the severe multisystem clinical phenotype seen in this baby and that mutations in LARS2 can result in variable phenotypes.
Identifiers
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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.