ArticlePLoS genetics2020
THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- TECTB Variants Reveal Tectorial Membrane Vulnerability in Dominant Non-Syndromic Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Precision Diagnostics in Age-Related Hearing Loss: Emerging Molecular Biomarkers for Early Detection and Targeted Prevention.International journal of general medicine · 2026Review
- Quercetin prevents age-related hearing loss in C57BL/6J mice by activating mitophagy and inhibiting the NLRP3 inflammasome.PloS one · 2026Article
- ThemedRxiv : the preprint server for health sciences · 2025Article
- Cdh23 Gene Mutation-Induced Vestibular Dysfunction in Mice: Abnormal Stereocilia Bundle and Otolith Development and Activation of p53/FoxO Signaling Pathway.Journal of molecular neuroscience : MN · 2025Article
- POLD3 haploinsufficiency is linked to non-syndromic sensorineural adult-onset progressive hearing and balance impairments.European journal of human genetics : EJHG · 2025Article
- Knockout ofBiomedicines · 2024Article
- Glycodiversification of gentamicins throughActa pharmaceutica Sinica. B · 2024Article
- A novel variant in GAS2 is associated with autosomal dominant nonsyndromic hearing impairment in a Chinese family.Human genomics · 2024Article
- Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.Biomedicines · 2023Review
- The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss.Cell & bioscience · 2023Review
- A novel recessive mutation in OXR1 is identified in patient with hearing loss recapitulated by the knockdown zebrafish.Human molecular genetics · 2023Article
- Gene therapy: an emerging therapy for hair cells regeneration in the cochlea.Frontiers in neuroscience · 2023Review
- Identification of 3-Phenylquinoline Derivative PQ1 as an Antagonist of p53 Transcriptional Activity.ACS omega · 2022Article
- Single-cell RNA-sequencing of zebrafish hair cells reveals novel genes potentially involved in hearing loss.Cellular and molecular life sciences : CMLS · 2022Article
- Multiplexed Genome Editing for Efficient Phenotypic Screening in Zebrafish.Veterinary sciences · 2022Article
- Involvement of the SIRT1/PGC-1α Signaling Pathway in Noise-Induced Hidden Hearing Loss.Frontiers in physiology · 2022Article
- SLC26A4 Mutation Promotes Cell Apoptosis by Inducing Pendrin Transfer, Reducing ClBioMed research international · 2022Article
- Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics.Frontiers in cellular neuroscience · 2022Article
- Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies.Genes · 2021Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis of cochlear hair cells is a key step towards age-related hearing loss. Although numerous genes have been implicated in the genetic causes of late-onset, progressive hearing loss, few show direct links to the proapoptotic process. By genome-wide linkage analysis and whole exome sequencing, we identified a heterozygous p.L183V variant in THOC1 as the probable cause of the late-onset, progressive, non-syndromic hearing loss in a large family with autosomal dominant inheritance. Thoc1, a member of the conserved multisubunit THO/TREX ribonucleoprotein complex, is highly expressed in mouse and zebrafish hair cells. The thoc1 knockout (thoc1 mutant) zebrafish generated by gRNA-Cas9 system lacks the C-startle response, indicative of the hearing dysfunction. Both Thoc1 mutant and knockdown zebrafish have greatly reduced hair cell numbers, while the latter can be rescued by embryonic microinjection of human wild-type THOC1 mRNA but to significantly lesser degree by the c.547C>G mutant mRNA. The Thoc1 deficiency resulted in marked apoptosis in zebrafish hair cells. Consistently, transcriptome sequencing of the mutants showed significantly increased gene expression in the p53-associated signaling pathway. Depletion of p53 or applying the p53 inhibitor Pifithrin-α significantly rescued the hair cell loss in the Thoc1 knockdown zebrafish. Our results suggested that THOC1 deficiency lead to late-onset, progressive hearing loss through p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.
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