ArticleHuman mutation2009
Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms?
Article in Human mutation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 3 of them syntheses that pooled it.
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Who cites it
74 citing papers in PubMed, 3 syntheses or guidelines pooled it, 150 citations in OpenAlex.
- Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels.Genome medicine · 2019Pooled it
- Assessment of the Clinical Benefit of Imaging in Children With Unilateral Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.JAMA otolaryngology-- head & neck surgery · 2019Pooled it
- Diagnostic Value of SLC26A4 Mutation Status in Hereditary Hearing Loss With EVA: A PRISMA-Compliant Meta-Analysis.Medicine · 2015Pooled it
- Mutational spectrum of SLC26A4 and SLC26A5 associated with hereditary hearing loss in Moroccan families.Human genomics · 2026Article
- Genetic heterogeneity in patients with enlarged vestibular aqueduct and Pendred syndrome.Molecular medicine (Cambridge, Mass.) · 2025Article
- Inhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants.International journal of molecular medicine · 2025Article
- Novel genetic determinants contribute to hearing loss in a central European cohort with enlarged vestibular aqueduct.Molecular medicine (Cambridge, Mass.) · 2025Article
- SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.Science advances · 2024Article
- Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024Article
- Functional Studies of Deafness-Associated Pendrin and Prestin Variants.International journal of molecular sciences · 2024Article
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- CHD7 variants associated with hearing loss and enlargement of the vestibular aqueduct.Human genetics · 2023Article
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- Selection of Diagnostically Significant Regions of theInternational journal of molecular sciences · 2022Article
- Molecular Features of SLC26A4 Common Variant p.L117F.Journal of clinical medicine · 2022Article
- Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss.Human genetics · 2022Review
- A newly identified mutation (c.2029 C > T) in SLC26A4 gene is associated with enlarged vestibular aqueducts in a Chinese family.BMC medical genomics · 2022Article
- Mutation Screening and Functional Study ofJournal of clinical research in pediatric endocrinology · 2022Article
- Atypical Presentation of Enlarged Vestibular Aqueducts Caused byChildren (Basel, Switzerland) · 2022Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 13 institutions in 1 country.
Funding
Abstract
Hearing loss with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene encoding pendrin, a transmembrane Cl(-)/I(-)/HCO(3)(-) exchanger. Pendrin's critical transport substrates are thought to be I(-) in the thyroid gland and HCO(3)(-) in the inner ear. We previously reported that bi-allelic SLC26A4 mutations are associated with Pendred syndromic EVA whereas one or zero mutant alleles are associated with nonsyndromic EVA. One study proposed a correlation of nonsyndromic EVA with SLC26A4 alleles encoding pendrin with residual transport activity. Here we describe the phenotypes and SLC26A4 genotypes of 47 EVA patients ascertained since our first report of 39 patients. We sought to determine the pathogenic potential of each variant in our full cohort of 86 patients. We evaluated the trafficking of 11 missense pendrin products expressed in COS-7 cells. Products that targeted to the plasma membrane were expressed in Xenopus oocytes for measurement of anion exchange activity. p.F335L, p.C565Y, p.L597S, p.M775T, and p.R776C had Cl(-)/I(-) and Cl(-)/HCO(3)(-) exchange rate constants that ranged from 13 to 93% of wild type values. p.F335L, p.L597S, p.M775T and p.R776C are typically found as mono-allelic variants in nonsyndromic EVA. The high normal control carrier rate for p.L597S indicates it is a coincidentally detected nonpathogenic variant in this context. We observed moderate differential effects of hypo-functional variants upon exchange of HCO(3)(-) versus I(-) but their magnitude does not support a causal association with nonsyndromic EVA. However, these alleles could be pathogenic in trans configuration with a mutant allele in Pendred syndrome.
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