Channelopathies are disorders caused by abnormal ion channel function in differentiated excitable tissues. We discovered a unique neurodevelopmental channelopathy resulting from pathogenic variants in SCN3A, a gene encoding the voltage-gated sodium channel NaV1.3. Pathogenic NaV1.3 channels showed altered biophysical properties including increased persistent current. Remarkably, affected individuals showed disrupted folding (polymicrogyria) of the perisylvian cortex of the brain but did not typically exhibit epilepsy; they presented with prominent speech and oral motor dysfunction, implicating SCN3A in prenatal development of human cortical language areas. The development of this disorder parallels SCN3A expression, which we observed to be highest early in fetal cortical development in progenitor cells of the outer subventricular zone and cortical plate neurons and decreased postnatally, when SCN1A (NaV1.1) expression increased. Disrupted cerebral cortical folding and neuronal migration were recapitulated in ferrets expressing the mutant channel, underscoring the unexpected role of SCN3A in progenitor cells and migrating neurons.
Pubmed ID: 30146301 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
National resource for investigators utilizing human post-mortem brain tissue and related biospecimens for their research to understand conditions of the nervous system. Federated network of brain and tissue repositories in the United States that collects, evaluates, stores, and makes available to researchers, brain and other tissues in a way that is consistent with the highest ethical and research standards. The NeuroBioBank ensures protection of the privacy and wishes of donors. Provides information to the public about the need for tissue donation and how to register as a donor.
View all literature mentionsDatabase that aggregates exome and genome sequencing data from large-scale sequencing projects. The gnomAD data set contains individuals sequenced using multiple exome capture methods and sequencing chemistries. Raw data from the projects have been reprocessed through the same pipeline, and jointly variant-called to increase consistency across projects.
View all literature mentionsThis monoclonal targets Na channel α subunits
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets ATP1A1
View all literature mentionsThis polyclonal targets SATB2
View all literature mentionsThis unknown targets RFP Antibody
View all literature mentionsThis monoclonal targets Neuron specific beta III Tubulin
View all literature mentionsThis polyclonal targets GFAP - Astrocyte Marker
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsThis monoclonal targets vimentin, phospho (Ser55)
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsSoftware used for visualizing and graphing data, image processing, and programming. It is designed for use by scientists and engineers and supports large data sets, evenly spaced data, and various data import formats. The software includes a suite of image processing operations for image filtering, manipulation, and quantification and is completely programmable.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsOpen source software suite for processing and analyzing human brain MRI images. Used for reconstruction of brain cortical surface from structural MRI data, and overlay of functional MRI data onto reconstructed surface. Contains automatic structural imaging stream for processing cross sectional and longitudinal data. Provides anatomical analysis tools, including: representation of cortical surface between white and gray matter, representation of the pial surface, segmentation of white matter from rest of brain, skull stripping, B1 bias field correction, nonlinear registration of cortical surface of individual with stereotaxic atlas, labeling of regions of cortical surface, statistical analysis of group morphometry differences, and labeling of subcortical brain structures.Operating System: Linux, macOS.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Na channel α subunits
View all literature mentions