| Autor: |
Chad O. Brown, Jarryll A. Uy, Nadeem Murtaza, Elyse Rosa, Alexandria Alfonso, Biren M. Dave, Savannah Kilpatrick, Annie A. Cheng, Sean H. White, Stephen W. Scherer, Karun K. Singh |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cellular Neuroscience, Vol 17 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1662-5102 |
| DOI: |
10.3389/fncel.2023.1239069 |
| Popis: |
SCN2A is an autism spectrum disorder (ASD) risk gene and encodes a voltage-gated sodium channel. However, the impact of ASD-associated SCN2A de novo variants on human neuron development is unknown. We studied SCN2A using isogenic SCN2A–/– induced pluripotent stem cells (iPSCs), and patient-derived iPSCs harboring a de novo R607* truncating variant. We used Neurogenin2 to generate excitatory (glutamatergic) neurons and found that SCN2A+/R607* and SCN2A–/– neurons displayed a reduction in synapse formation and excitatory synaptic activity. We found differential impact on actional potential dynamics and neuronal excitability that reveals a loss-of-function effect of the R607* variant. Our study reveals that a de novo truncating SCN2A variant impairs the development of human neuronal function. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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