Two CaV3.3 (CACNA1I) Gain-of-Function Mutations Linked to Epilepsy and Intellectual Disability Affect Gating Properties and the Window Current

T-type calcium channels are important for neuronal burst firing and rhythmic oscillations, and implicated in various neurological diseases. We examined two missense variants in CACNA1I encoding the CaV3.3 channel that, for the first time, link CACNA1I to epilepsy and intellectual disability (ID). Both mutations affect the same amino acid residue (I860) located in the putative activation gate. I860N is a de novo variant identified in a girl with...