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Sodium Channel SCN3A (Na V 1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development.
- Source :
-
Neuron [Neuron] 2018 Sep 05; Vol. 99 (5), pp. 905-913.e7. Date of Electronic Publication: 2018 Aug 23. - Publication Year :
- 2018
-
Abstract
- 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 Na <subscript>V</subscript> 1.3. Pathogenic Na <subscript>V</subscript> 1.3 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 (Na <subscript>V</subscript> 1.1) 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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Animals
Cell Movement physiology
Cells, Cultured
Cerebral Cortex pathology
Child
Child, Preschool
Female
Ferrets
HEK293 Cells
Humans
Infant
Male
Megalencephaly diagnostic imaging
Megalencephaly genetics
Megalencephaly pathology
Middle Aged
Pedigree
Polymicrogyria diagnostic imaging
Polymicrogyria genetics
Polymicrogyria pathology
Cerebral Cortex diagnostic imaging
Cerebral Cortex growth & development
Language Development
NAV1.3 Voltage-Gated Sodium Channel genetics
Sodium Channels genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 99
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 30146301
- Full Text :
- https://doi.org/10.1016/j.neuron.2018.07.052