Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: SLC26A4 is the second most common cause of hereditary hearing loss worldwide. This gene predominantly harbors pathogenic variants, including splice, nonsense, and missense. Although missense variants are relatively common, their specific effects on protein function remain unclear. Consequently, there is an urgent need to establish an in vitro system to investigate how these variants impact SLC26A4 protein function.
Methods: Genetic testing was conducted to determine the specific types of underlying genetic variants in patients. Following this, we employed plasmid transfection to evaluate the effects of the variants on both protein expression levels and the protein's subcellular localization. Thereafter, we transformed peripheral blood mononuclear cells (PBMCs) from the proband into induced pluripotent stem cells (iPSCs) through Sendai virus-mediated transduction.
Results: Genetic testing revealed that the proband carried compound heterozygous variants: SLC26A4 c.919-2A > G and c.317C > A. The c.317C > A variant markedly decreased the expression levels of SLC26A4 mRNA and its encoded protein. Additionally, it led to the protein's accumulation in the cytoplasm as aggregates. We successfully reprogrammed peripheral blood mononuclear cells from the proband into induced pluripotent stem cells (iPSCs) and verified that these iPSCs retained their pluripotency, differentiation potential, and genetic integrity.
Conclusion: These results provide important insights into the mechanisms by which SLC26A4 gene variants lead to hearing loss.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012755 | PMC |
| http://dx.doi.org/10.1002/mgg3.70098 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
P2X7 receptor antagonism suppresses epileptiform-like activity in an inflammation-primed human iPSC-derived neuron model of drug-resistant epilepsy.
Br J Pharmacol
September 2025
Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Background And Purpose: Neuroinflammation is increasingly recognised to contribute to drug-resistant epilepsy. Activation of ATP-gated P2X7 receptors has emerged as an important upstream mechanism, and increased P2X7 receptor expression is present in the seizure focus in rodent models and patients. Pharmacological antagonists of P2X7 receptors attenuate seizures in rodents, but this has not been explored in human neural networks.
View Article and Find Full Text PDFABCA7 variants impact phosphatidylcholine and mitochondria in neurons.
Nature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFBMAL1-TRIM28 represses transposable elements independently of CLOCK in pluripotent cells.
Nat Commun
September 2025
Centre for Genomics and Oncological Research (GENYO), Avenue de la Ilustración 114, 18016, Granada, Spain.
Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show that BMAL1 interacts with TRIM28 and facilitates H3K9me3-mediated repression of transposable elements in naïve pluripotent cells, and that the loss of BMAL1 function induces a widespread transcriptional activation of MERVL elements, 3D genome reorganization and the acquisition of totipotency-associated molecular and cellular features.
View Article and Find Full Text PDFEstradiol alleviates disease phenotypes caused by m.3635G > a mutations by activating mitochondrial biogenesis and PINK1-Parkin mediated mitophagy in iPSC-derived retinal pigment epithelium cells.
Cell Signal
September 2025
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, China; Engin
Leber's hereditary optic neuropathy (LHON), a mitochondrial disorder marked by central vision loss, exhibits incomplete penetrance and male predominance. Since there are no adequate models for understanding the rapid vision loss associated with LHON, we generated induced pluripotent stem cells (iPSCs) from LHON patients carrying the pathogenic m.3635G > A mutation and differentiated them into retinal pigment epithelium (RPE) cells.
View Article and Find Full Text PDFExploring the potential pathogenesis of migraine using glutamatergic neuron models derived from induced pluripotent stem cells (iPSCs) of migraine patients.
Brain Res
September 2025
Department of Neurology, Shanghai Sixth People's Hospital, Shanghai 200233, China. Electronic address:
Migraine is a complex neurological disorder influenced by multiple genetic susceptibility factors, yet current animal models fail to fully recapitulate its human-specific pathophysiology. In this study, we explored the potential mechanisms underlying migraine by examining functional abnormalities and molecular dysregulation in glutamatergic neurons derived from induced pluripotent stem cells (iPSCs) of migraine patients. As key excitatory cells in the central nervous system, glutamatergic neurons are implicated in migraine through altered excitability, ion channel dysfunction, and dysregulation of nociceptive signaling molecules.
View Article and Find Full Text PDF