1. Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy
- Author
-
Souza, Ivana A, Gandini, Maria A, Zhang, Fang-Xiong, Mitchell, Wendy G, Matsumoto, Joyce, Lerner, Jason, Pierson, Tyler Mark, and Zamponi, Gerald W
- Subjects
Epilepsy ,Neurodegenerative ,Brain Disorders ,Neurosciences ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Biophysical Phenomena ,Calcium Channels ,T-Type ,Child ,Epilepsy ,Generalized ,Female ,Humans ,Infant ,Infant ,Newborn ,Mutation ,Cav3 ,2 ,T-type ,Seizure ,Cav3.2 ,Medical and Health Sciences ,Neurology & Neurosurgery - Abstract
Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile.
- Published
- 2019