Sodium Channel SCN3A (Na_V1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development.

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_V1.3. Pathogenic Na_V1.3 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 corti

SUBMITTER: Smith RS 

PROVIDER: S-EPMC6226006 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature