ArticleScientific reports2018
Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 27 citations in OpenAlex.
- HAP1 interaction with KCNQ4 attenuates channel surface expression and function.Molecules and cells · 2026Article
- Novel Variant inCells · 2023Article
- Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.Biomedicines · 2023Review
- Overlooked KCNQ4 variants augment the risk of hearing loss.Experimental & molecular medicine · 2023Article
- Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression.International journal of molecular sciences · 2023Article
- [The genotype-phenotype correlation analysis and genetic counseling of hearing loss patients with novelLin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2023Article
- The Pathological Mechanisms of Hearing Loss Caused byBiomedicines · 2022Review
- Predicting the functional effects of voltage-gated potassium channel missense variants with multi-task learning.EBioMedicine · 2022Article
- Exome sequencing of families from Ghana reveals known and candidate hearing impairment genes.Communications biology · 2022Article
- AudioGene: refining the natural history of KCNQ4, GSDME, WFS1, and COCH-associated hearing loss.Human genetics · 2022Article
- Article
- Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss.Scientific reports · 2021Article
- Bioelectric signaling as a unique regulator of development and regeneration.Development (Cambridge, England) · 2021Review
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss.International journal of molecular sciences · 2021Review
- Synergistic effect of smoking on age-related hearing loss in patients with diabetes.Scientific reports · 2020Article
- Computational analysis based on audioprofiles: A new possibility for patient stratification in office-based otology.Audiology research · 2019Article
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Authors and funding
15 authors at 2 institutions in 1 country.
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Abstract
Mutations in potassium voltage-gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to a type of nonsyndromic hearing loss, deafness nonsyndromic autosomal dominant 2 (DFNA2). We performed whole-exome sequencing for 98 families with hearing loss and found mutations in KCNQ4 in five families. In this study, we characterized two novel mutations in KCNQ4: a missense mutation (c.796G>T; p.Asp266Tyr) and an in-frame deletion mutation (c.259_267del; p.Val87_Asn89del). p.Asp266Tyr located in the channel pore region resulted in early onset and moderate hearing loss, whereas p.Val87_Asn89del located in the N-terminal cytoplasmic region resulted in late onset and high frequency-specific hearing loss. When heterologously expressed in HEK 293 T cells, both mutant proteins did not show defects in protein trafficking to the plasma membrane or in interactions with wild-type (WT) KCNQ4 channels. Patch-clamp analysis demonstrated that both p.Asp266Tyr and p.Val87_Asn89del mutant channels lost conductance and were completely unresponsive to KCNQ activators, such as retigabine, zinc pyrithione, and ML213. Channels assembled from WT-p.Asp266Tyr concatemers, like those from WT-WT concatemers, exhibited conductance and responsiveness to KCNQ activators. However, channels assembled from WT-p.Val87_Asn89del concatemers showed impaired conductance, suggesting that p.Val87_Asn89del caused complete loss-of-function with a strong dominant-negative effect on functional WT channels. Therefore, the main pathological mechanism may be related to loss of K
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