ArticleAmerican journal of human genetics2013
Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 112 citations in OpenAlex.
- Neuropathologic Features of Adult-Onset Progressive Leukodystrophy Due toNeurology. Genetics · 2026Article
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- Hyperkinetic Movement Disorder inNeurology international · 2025Article
- 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
- 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
- Article
- A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants.HGG advances · 2024Article
- Clinical Genetic Testing for Hearing Loss: Implications for Genetic Counseling and Gene-Based Therapies.Biomedicines · 2024Article
- Autosomal recessive non-syndromic hearing loss genes in Pakistan during the previous three decades.Journal of cellular and molecular medicine · 2024Review
- Predictive modeling provides insight into the clinical heterogeneity associated withbioRxiv : the preprint server for biology · 2024Article
- Antibody Deficiency in Patients with Biallelic KARS1 Mutations.Journal of clinical immunology · 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
- Cytoplasmic and mitochondrial aminoacyl-tRNA synthetases differentially regulate lifespan iniScience · 2022Article
- Article
- ARNSHL gene identification: past, present and future.Molecular genetics and genomics : MGG · 2022Review
- Report of rare and novel mutations in candidate genes in a cohort of hearing-impaired patients.Molecular genetics & genomic medicine · 2022Article
- Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population.Frontiers in genetics · 2022Article
- Aminoacyl-tRNA synthetases in human health and disease.Frontiers in physiology · 2022Review
- Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Previously, DFNB89, a locus associated with autosomal-recessive nonsyndromic hearing impairment (ARNSHI), was mapped to chromosomal region 16q21-q23.2 in three unrelated, consanguineous Pakistani families. Through whole-exome sequencing of a hearing-impaired individual from each family, missense mutations were identified at highly conserved residues of lysyl-tRNA synthetase (KARS): the c.1129G>A (p.Asp377Asn) variant was found in one family, and the c.517T>C (p.Tyr173His) variant was found in the other two families. Both variants were predicted to be damaging by multiple bioinformatics tools. The two variants both segregated with the nonsyndromic-hearing-impairment phenotype within the three families, and neither mutation was identified in ethnically matched controls or within variant databases. Individuals homozygous for KARS mutations had symmetric, severe hearing impairment across all frequencies but did not show evidence of auditory or limb neuropathy. It has been demonstrated that KARS is expressed in hair cells of zebrafish, chickens, and mice. Moreover, KARS has strong localization to the spiral ligament region of the cochlea, as well as to Deiters' cells, the sulcus epithelium, the basilar membrane, and the surface of the spiral limbus. It is hypothesized that KARS variants affect aminoacylation in inner-ear cells by interfering with binding activity to tRNA or p38 and with tetramer formation. The identification of rare KARS variants in ARNSHI-affected families defines a gene that is associated with ARNSHI.
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