AUTHOR=Hu Xiaoyue , Jing Miao , Wang Yanping , Liu Yanshan , Hua Ying 

TITLE=Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=16

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1159649

DOI=10.3389/fnmol.2023.1159649

ISSN=1662-5099

ABSTRACT=<sec><title>Objective</title><p>We admitted a female patient with infantile onset epilepsy (&lt;3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlations among genotype, phenotype, and clinical drug response.</p></sec><sec><title>Methods</title><p>We described the clinical characteristics of an infant with refractory epilepsy. Whole exome sequencing (WES) was used to screen for the pathogenic variant. Whole-cell patch-clamp was performed to determine functional outcomes of the variant.</p></sec><sec><title>Results</title><p>WES identified a novel <italic>de novo SCN2A</italic> variant (c.468 G &gt; C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that <italic>SCN2A</italic>-K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na<sup>+</sup> channel, all of which suggested a loss-of-function (LOF) of Na<sub>v</sub>1.2 channel.</p></sec><sec><title>Conclusion</title><p>We showed the importance of functional analysis for a <italic>SCN2A</italic> variant with unknown significance to determine pathogenicity, drug reactions, and genotype–phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some <italic>SCN2A</italic>-related epilepsies requires vigilance to assess the possibility of epilepsy worsening.</p></sec>