Mechanism of Two Novel Human GJC3 Missense Mutations in Causing Non-Syndromic Hearing Loss

Su, Chin-Chuan; Li, Shuan‐Yow; Yen, Yung-Chang; Nian, Jhih-Hao; Liang, Wei-Guang; Yang, Jiann‐Jou

doi:10.1007/s12013-012-9481-8

Cited by 11 publications

(14 citation statements)

References 51 publications

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“…1A and 1B). These results are consistent with our previous studies 18-19. Contrary to CX30.2/CX31.3WT, as seen in the immunolabeling assay, CX30.2/CX31.3W77S mutant proteins were concentrated in the cytoplasm close to the nucleus (Fig.…”

Section: Resultssupporting

confidence: 93%

“…We found that the topological model of CX30.2/CX31.3 protein is similarily other members of CX family. The structure of CX30.2/CX31.3 protein was described previously 19 and was displyed in supplemental Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, we have found that p.E269D mutation in the GJC3 gene has a dominant negative effect on the formation and function of the gap junction 18. In addition, we found that p.R15G and p.L23H mutants do not decrease the trafficking of CX proteins, but the mutations in GJC3 genes result in a loss of function of the CX30.2/CX31.3 protein 19. However, the functional alternation of CX30.2/CX31.3 caused by the p.W77S mutant remains unclear.…”

Section: Introductionmentioning

confidence: 82%

“…After removing the nonadherent dead cells in the cultures by rinsing with PBS, the adherent cells were collected by centrifugation for 5 min (1000 rpm) at room temperature. DNAs were purified as previously describe 19. Different DNA concentrations from 500μg to 3000μg were resolved in a 1 % (w/v) agarose gel in 1x TAE buffer.…”

Section: Methodsmentioning

confidence: 99%

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Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene

Wong¹,

Wang²,

Chen³

et al. 2017

Int. J. Med. Sci.

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In a previous study, we identified a novel missense mutation, p.W77S, in the GJC3 gene encoding connexin30.2/connexin31.3 (CX30.2/CX31.3) from patients with hearing loss. The functional alteration of CX30.2/CX31.3 caused by the p.W77S mutant of GJC3 gene, however, remains unclear. In the current study, our result indicated that the p.W77 is localized at the second membrane-spanning segments (TM2) and near border of the E1 domain of the CX30.2/CX31.3 protein and highly conserved (Conseq score = 8~9) in all species. The p.W77S missense mutation proteins in the intracellular distribution are different CX30.2/CX31.3WT and an accumulation of the mutant protein in the endoplasmic reticulum (ER) of the HeLa cell. Furthermore, co-expression of WT and p.W77S mutant chimerae proteins showed that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the WT proteins' expression in the cell membranes. In addition, we found that CX30.2/CX31.3W77S missense mutant proteins were degraded by lysosomes and proteosomes in the transfected HeLa cell. Based on these findings, we suggest that p.W77S mutant has a dominant negative effect on the formation and function of the gap junction. These results give a novel molecular elucidation for the mutation of GJC3 in the development of hearing loss.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

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Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene

Wong¹,

Wang²,

Chen³

et al. 2017

Int. J. Med. Sci.

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“…We identified six positively selected genes ( Fig. 1) that conceivably evolved to increase auditory acuity over a wider range of frequencies in the carnivore ancestor and within Felidae, as mutations within each gene have been associated with autosomal, nonsyndromic deafness or hearing loss (22,23). Visual acuity is adaptive for hunting and catching prey, especially for crepuscular predators such as the cat and other carnivores.…”

Section: Resultsmentioning

confidence: 99%

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Montague

Gandolfi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

285

269

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Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.Felis catus | domestication | genome T he domestic cat (Felis silvestris catus) is a popular pet species, with as many as 600 million individuals worldwide (1). Cats and other members of Carnivora last shared a common ancestor with humans ∼92 million years ago (2, 3). The cat family Felidae includes ∼38 species that are widely distributed across the world, inhabiting diverse ecological niches that have resulted in divergent morphological and behavioral adaptations (4). The earliest archaeological evidence for human coexistence with cats dates to ∼9.5 kya in Cyprus and ∼5 kya in central China (5, 6), during periods when human populations adopted more agricultural lifestyles. Given their sustained beneficial role surrounding vermin control since the human transition to agriculture, any selective forces acting on cats may have been minimal subsequent to their domestication. Unlike many other domesticated mammals bred for food, herding, hunting, or security, most of the 30-40 cat breeds originated recently, within the past 150 y, largely due to selection for aesthetic rather than functional traits.Previous studies have assessed breed differentiation (6, 7), phylogenetic origins of the domestic cat (8), and the extent of recent introgression between domestic cats and wildcats (9, 10). However, little is known regarding the impact of the domestication process within the genomes of modern cats and how this compares with genetic changes accompanying selection identified...

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Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

Lin

Shen

et al. 2020

Molecular Oncology

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Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407 TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30-2.09, P = 4.52 9 10 À5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87-1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407 TRIM27 methylation in NSCLC. LUSC patients had a higher average pack-year of smoking

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Mechanism of Two Novel Human GJC3 Missense Mutations in Causing Non-Syndromic Hearing Loss

Cited by 11 publications

References 51 publications

Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene

Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene

Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

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