ArticleHuman genetics2021
A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans.
Article in Human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- PALM3 and hearing loss: a potential dual diagnosis interfering with novel gene discovery.European journal of human genetics : EJHG · 2026Article
- Molecular identity of the mechanotransduction machinery in inner ear hair cells and mechanotransduction-linked hearing loss.Fundamental research · 2026Review
- Compensatory Interplay Between Clarin-1 and Clarin-2 Deafness-Associated Proteins Governs Phenotypic Variability in Hearing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-ancestry GWAS of age-related hearing loss identifies 140 loci and key cellular mechanisms.Nature communications · 2026Article
- Hearing loss: a global view for gene therapy approaches and challenges.European journal of pediatrics · 2025Review
- Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons.Cell reports · 2025Article
- The P4-phospholipid flippase Atp11a is required for maintenance of eye and ear structure in zebrafish.Journal of cell science · 2025Article
- A novel CLRN2 variant: expanding the mutation spectrum and its critical role in isolated hearing impairment.Genes & genomics · 2025Article
- Defects in hair cells disrupt the development of auditory peripheral circuitry.Nature communications · 2024Article
- Clarin-2 gene supplementation durably preserves hearing in a model of progressive hearing loss.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss.Human genetics · 2024Article
- Article
- Mechanoelectrical transduction-related genetic forms of hearing loss.Current opinion in physiology · 2023Article
- Syntaxin 4 is essential for hearing in human and zebrafish.Human molecular genetics · 2023Article
- In-depth genetic and molecular characterization of diaphanous related formin 2 (DIAPH2) and its role in the inner ear.PloS one · 2023Article
- Unraveling haplotype errors in the DFNA33 locus.Frontiers in genetics · 2023Article
- TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia.Brain : a journal of neurology · 2022Article
- ARNSHL gene identification: past, present and future.Molecular genetics and genomics : MGG · 2022Review
- Genetic etiology of hearing loss in Iran.Human genetics · 2022Review
- Usher syndrome IIIA: a review of the disorder and preclinical research advances in therapeutic approaches.Human genetics · 2022Review
Corrections and comments
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Authors and funding
26 authors at 12 institutions in 5 countries.
Funding
Abstract
Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.
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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.