Authors:

Hina Leilani Kadono

Date Created:

Not specified

Course Title:

Professor:

Not specified

About Paper:

The SCN2A gene encodes for the voltage-gated sodium channel alpha subunit NaV1.2, which is widely expressed in the brain and essential for neuronal function. Approximately 300 genetic variants within the SCN2A gene have been identified, many of which are linked to neurodevelopmental disorders such as autism spectrum disorder (ASD) and epileptic encephalopathy (EE). However, the mechanisms underlying the effects of many of these variants remain not fully understood. Our research aims to gain a deeper understanding of one of these variants by investigating a novel splice-site variant in SCN2A identified in a child with ASD. To characterize the phenotypes associated with this variant, we introduced the splice-site variant into a reference human induced pluripotent stem cell (hiPSC) line, which was then differentiated into cortical organoids expressing the NaV1.2 channel. We generated three batches of organoids: one homozygous for the variant, one heterozygous for the variant, and a wild-type batch not carrying the variant. For this study, these organoid batches were subjected to immunocytochemistry to identify differences in neural rosettes, which are key morphological characteristics of cortical organoids as they are developmental markers of neuroprogenitors in differentiating hiPSCs. Currently, we are focusing on quantifying the number of rosettes and analyzing their sizes within these organoids. By comparing data obtained from the organoids carrying the variant with the wild- type organoids, we aim to identify significant differences. Our findings will reveal the phenotypic changes caused by this splice-site variant, which will aid in the future development of personalized therapeutic interventions. Keywords: Autism; Sodium Channel; SCN2A; hiPSC; Organoid

Source:

Purdue University / 2024

Topics:

No topics listed

Co-authors:

Hina Leilani Kadono