Identification and Characterization of a Novel CACNA1A Variant in Epileptic Encephalopathy

This is the authors' abstract. We don't add key points for this paper.

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.