Population
Human induced pluripotent stem cell (iPSC)-derived excitatory neurons modeling KCNQ2 encephalopathy
Comparison
Gene editing to establish a disease model and… vs Control neurons
Design
Preclinical
Key result
Patient iPSC-derived neurons with the KCNQ2 R581Q mutation exhibited progressive escalation of burst firing, faster action potential repolarization, and larger post-burst afterhyperpolarization compared to isogenic controls.
Authors
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iPSC neuron phenotypes suggest compensatory K+ channel changes in KCNQ2 disorders; leaves open translation to in vivo mechanisms or therapies.
Dyshomeostatic mechanisms compound KCNQ2 loss-of-function, altering the neurodevelopmental trajectory and electrophysiological properties of patient iPSC-derived neurons.
p-value: p=<0.0001
Simkin et al. (2021) studied KCNQ2 epileptic encephalopathy (n=4). KCNQ2 R581Q mutation vs. Isogenic mutation-corrected control neurons was evaluated on Spontaneous neuronal activity and burst firing (p=<0.0001). Patient iPSC-derived neurons with the KCNQ2 R581Q mutation exhibited progressive escalation of burst firing, faster action potential repolarization, and larger post-burst afterhyperpolarization compared to isogenic controls.