De Novo ACTB Variant Associated With Juvenile-Onset Temporal Lobe Epilepsy With Favorable Outcomes

Abstract

Genetic factors are estimated to contribute to 80% of people with epilepsy. However, only four genes were reported to be associated with temporal lobe epilepsy (TLE). This study is aimed at investigating the association between ACTB and TLE. Trio-based exome sequencing was performed in a patient, and a de novo ACTB variant was identified. The patient presented with TLE featuring by age of onset in juvenile, seizure-free status in adulthood, complications of memory decline and irritability, epileptic discharges in the bilateral temporal lobes, and bilateral hippocampal sclerosis. The pathogenicity of the identified ACTB variant was supposed by multiple pieces of evidence, including the missense tolerance ratio of 0%, high conservation of the affected residue, predicted to be “damaging” or “conserved” by 17 in silico tools, and classification of likely pathogenic variant by the American College of Medical Genetics and Genomics (ACMG) guidelines. Protein modeling indicated the alteration of protein structure and stability caused by the identified variant. The spatiotemporal expression of ACTB is consistent with the phenotypic features of this patient. This study suggested that ACTB is a novel candidate causative gene of TLE. The correlation between phenotypes and spatial–temporal expression provides a novel perspective for further exploration of the pathogenesis and prognosis of the disease.