CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy
- 1Boston Children's Hospital
Abstract
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 non-centrosomal microtubule dynamics, and the acetylation necessary for normal axonal differentiation and migration. We show that overexpression of patient variants leads to protein degradation and dysregulation of microtubule acetylation in cultured HEK cells. Camsap3 knockout zebrafish also exhibit increased axonal microtubule acetylation as well as epileptic features such as seizure-like swimming behaviors, aberrant inhibitory interneuron development and epileptiform via local field potential. Together these data suggest that CAMSAP3 plays an important role in generalized genetic epilepsy.
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BibTeX
@misc{lacoursiere2026camsap3,
title = {{CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy}},
author = {C. M. LaCoursiere and Z. Stayn and H. Hepner and S. Tiwari and J. Pascucci and C. Moschopoulos and L. Smith and H. Y. Koh and P. Chaudhary and A. Poduri},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.744686},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.744686v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - CAMSAP3 loss of function models suggest causative role in generalized genetic epilepsy
AU - C. M. LaCoursiere
AU - Z. Stayn
AU - H. Hepner
AU - S. Tiwari
AU - J. Pascucci
AU - C. Moschopoulos
AU - L. Smith
AU - H. Y. Koh
AU - P. Chaudhary
AU - A. Poduri
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.744686
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.744686v1
AB - 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 non-centrosomal microtubule dynamics, and the acetylation necessary for normal axonal differentiation and migration. We show that overexpression of patient variants leads to protein degradation and dysregulation of microtubule acetylation in cultured HEK cells. Camsap3 knockout zebrafish also exhibit increased axonal microtubule acetylation as well as epileptic features such as seizure-like swimming behaviors, aberrant inhibitory interneuron development and epileptiform via local field potential. Together these data suggest that CAMSAP3 plays an important role in generalized genetic epilepsy.
ER -