ArticleHuman molecular genetics2006
Pathogenetic role of the deafness-related M34T mutation of Cx26.
Article in Human molecular genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels.Genome medicine · 2019Pooled it
- Genome-wide CRISPR screening identifies cellular factors controlling nonviral genome editing efficiency.Nature communications · 2026Article
- The Cochlear Lateral Wall as a Biological Battery: the Mechanisms Underlying KJournal of the Association for Research in Otolaryngology : JARO · 2026Review
- Model-based evaluation of connexin hemichannel permeability.Computational and structural biotechnology journal · 2025Article
- Functional Consequences of Pathogenic Variants of theBiomolecules · 2023Review
- Global Distribution of Founder Variants Associated with Non-Syndromic Hearing Impairment.Genes · 2023Review
- Connexin Mutations and Hereditary Diseases.International journal of molecular sciences · 2022Review
- A deep convolutional neural network for segmentation of whole-slide pathology images identifies novel tumour cell-perivascular niche interactions that are associated with poor survival in glioblastoma.British journal of cancer · 2021Article
- Functional Evaluation of a Rare Variant c.516G>C (p.Trp172Cys) in theBiomolecules · 2021Article
- Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease.Frontiers in genetics · 2019Article
- Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity.Computational biology and chemistry · 2018Article
- Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss.Human mutation · 2018Article
- Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia.Medicina (Kaunas, Lithuania) · 2018Article
- DFNB1 Non-syndromic Hearing Impairment: Diversity of Mutations and Associated Phenotypes.Frontiers in molecular neuroscience · 2017Review
- Altered CO2 sensitivity of connexin26 mutant hemichannels in vitro.Physiological reports · 2016Article
- The unique electrical properties in an extracellular fluid of the mammalian cochlea; their functional roles, homeostatic processes, and pathological significance.Pflugers Archiv : European journal of physiology · 2016Review
- Connexinopathies: a structural and functional glimpse.BMC cell biology · 2016Review
- The high frequency of GJB2 gene mutation c.313_326del14 suggests its possible origin in ancestors of Lithuanian population.BMC genetics · 2016Observational
- Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.Experimental & molecular medicine · 2015Article
- Connexins and gap junctions in the inner ear--it's not just about K⁺ recycling.Cell and tissue research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
Mutations in the GJB2 gene, which encodes the gap junction protein connexin26 (Cx26), are the major cause of genetic non-syndromic hearing loss. The role of the allelic variant M34T in causing hereditary deafness remains controversial. By combining genetic, clinical, biochemical, electrophysiological and structural modeling studies, we have re-assessed the pathogenetic role of the M34T mutation. Genetic and audiological data indicate that the majority of heterozygous carriers and all five compound heterozygotes exhibited an impaired auditory function. Functional expression in transiently transfected HeLa cells showed that, although M34T was correctly synthesized and targeted to the plasma membrane, it inefficiently formed intercellular channels that displayed an abnormal electrical behavior and retained only 11% of the unitary conductance of the wild-type protein (HCx26wt). Moreover, M34T channels failed to support the intercellular diffusion of Lucifer Yellow and the spreading of mechanically induced intercellular Ca2+ waves. When co-expressed together with HCx26wt, M34T exerted dominant-negative effects on cell-cell coupling. Our findings are consistent with a structural model, predicting that the mutation leads to a constriction of the channel pore. These data support the view that M34T is a pathological variant of Cx26 associated with hearing impairment.
Indexed as
Identifiers
What OpenQuestion holds
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.