CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy
Advancements in next generation sequencing have led to the discovery of hundreds of human epilepsy gene associations. Newly associated genes require functional validation to establish causation and to inform patient treatment in the clinic. A recent exome trio analysis identified predicted pathogenic variants in two patients with generalized epilepsy in the gene CAMSAP3. CAMSAP3 regulates…
Recent research utilizing next generation sequencing has identified several genes associated with epilepsy. Validation of these genes is crucial to establish causation and guide clinical treatment. In a recent study, two patients with generalized epilepsy were found to have predicted pathogenic variants in the CAMSAP3 gene. CAMSAP3 is known to regulate non-centrosomal microtubule dynamics, which are essential for normal axonal differentiation and migration.
The researchers observed that overexpression of the patient variants in cultured HEK cells results in protein degradation and dysregulation of microtubule acetylation. Similarly, zebrafish knockouts of CAMSAP3 also display increased axonal microtubule acetylation along with epileptic characteristics. These seizures manifest as swimming behaviors, altered inhibitory interneuron development, and epileptiform patterns as seen in local field potentials.
These findings collectively point towards an important role of CAMSAP3 in generalized genetic epilepsy.
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