Identification and Characterization of a Novel CACNA1A Variant in Epileptic Encephalopathy

Genetic mutations in CACNA1A are associated with severe forms of epileptic encephalopathy. The CACNA1A gene encodes the alpha-1 subunit of the voltage-gated calcium channel CaV2.1 (P/Q-type), which is critical for synaptic transmission and neuronal excitability. Pathogenic variants in this gene have been associated with early-onset epileptic encephalopathies such as Ohtahara syndrome, Lennox-Gastaut syndrome, and autosomal dominant developmental and epileptic encephalopathy. The aim of the study was to identify pathogenic CACNA1A variants in patients with developmental and epileptic encephalopathy and to characterize a new pathogenic variant in this gene. We assessed the clinical and genetic implications of a newly identified variant c.2134G>T (p.Ala712Ser), which expands the mutational spectrum of CACNA1A-associated epileptic encephalopathies. Comparative analysis of this variant with the known pathogenic variant c.2134G>A (p.Ala712Thr) reveals common and distinctive clinical features between the two patients, highlighting the role of the studied amino acid residue in the development of neurological diseases.