ArticlePLoS genetics2015
Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Cochlear Implantation Outcomes in Post Synaptic Auditory Neuropathies: A Systematic Review and Narrative Synthesis.The journal of international advanced otology · 2020Pooled it
- The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy.Journal of human genetics · 2018Trial
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Retrocochlear Auditory Dysfunctions (RADs) and Their Treatment: A Narrative Review.Audiology research · 2025Review
- Neonatal diabetes mellitus is a significant feature of COXPD-24 caused by recessive NARS2 variants.Diabetic medicine : a journal of the British Diabetic Association · 2025Article
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- A novel BCAP31 variant associated with nonsyndromic auditory neuropathy spectrum disorder: mitochondrial dysfunction, cisplatin sensitivity, and amenability to mitochondrial transplantation.Journal of translational medicine · 2025Article
- Compound heterozygous variants of theFrontiers in pediatrics · 2025Article
- Stroke-like lesion and status epilepticus in a child withFrontiers in neurology · 2025Article
- Article
- Article
- Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades.Journal of cellular and molecular medicine · 2024Review
- Novel NARS2 variants in a patient with early-onset status epilepticus: case study and literature review.BMC pediatrics · 2024Review
- The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study.Frontiers in cell and developmental biology · 2024Article
- Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis.Molecular neurobiology · 2023Review
- Article
- Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.Human genetics · 2023Article
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease.Genes · 2022Review
- Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease.Nucleic acids research · 2022Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
38 authors at 19 institutions in 6 countries.
Funding
Abstract
Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.Val213Phe]) is the underlying cause of nonsyndromic hearing loss (DFNB94) and compound heterozygous mutations ([c.969T>A; p.Tyr323*] + [c.1142A>G; p.Asn381Ser]) result in mitochondrial respiratory chain deficiency and Leigh syndrome, which is a neurodegenerative disease characterized by symmetric, bilateral lesions in the basal ganglia, thalamus, and brain stem. The severity of the genetic lesions and their effects on NARS2 protein structure cosegregate with the phenotype. A hypothetical truncated NARS2 protein, secondary to the Leigh syndrome mutation p.Tyr323* is not detectable and p.Asn381Ser further decreases NARS2 protein levels in patient fibroblasts. p.Asn381Ser also disrupts dimerization of NARS2, while the hearing loss p.Val213Phe variant has no effect on NARS2 oligomerization. Additionally we demonstrate decreased steady-state levels of mt-tRNAAsn in fibroblasts from the Leigh syndrome patients. In these cells we show that a decrease in oxygen consumption rates (OCR) and electron transport chain (ETC) activity can be rescued by overexpression of wild type NARS2. However, overexpression of the hearing loss associated p.Val213Phe mutant protein in these fibroblasts cannot complement the OCR and ETC defects. Our findings establish lesions in NARS2 as a new cause for nonsyndromic hearing loss and Leigh syndrome.
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.