Posters

Background: Status epilepticus (SE) is a neurological emergency associated with high morbidity and mortality, yet the early molecular changes accompanying sustained seizure activity remain incompletely understood. Heterogeneity between gene expression studies of animal SE models warrants a robust comparison to define the transcriptomic profile of SE across platforms, species, and experimental models.

Methods: We performed a meta-analysis of published gene expression studies of animal SE models encompassing the first 72 hours following SE onset. Twelve studies, comprising 37 transcriptomic datasets, were included, spanning species (mouse, rat) and experimental model (kainic acid, pilocarpine, self-sustaining SE). Pre-defined time windows (0-12, 12-24, 24-72 hours) were used to improve temporal resolution. Datasets were harmonised, mapped to human orthologues and analysed using multilevel linear mixed-effects models.

Results: Across all datasets, 444,693 animal gene entries mapped to human orthologs, yielding 17,215 unique human genes. Global analysis across time windows and SE models identified 118 differentially expressed genes (112 upregulated and 6 downregulated). Temporal analysis demonstrated largely distinct transcriptional profiles across time windows, with 83-87% of DEGs specific to their respective window. Four genes (FOS, TUBB6, TIMP1, HSPB1) were persistently upregulated across the first 24 hours following onset. Model-stratified analysis revealed distinct transcriptomic profiles across SE models. Pathway enrichment analysis identified early enrichment of inflammatory signalling pathways, including interleukin-17 (IL-17) signalling.

Conclusions: We provide a comprehensive molecular overview of early SE and show it be characterised by a highly dynamic, time-dependent transcriptomic response, with a small core of conserved dysregulated genes and prominent activation of pro-inflammatory cascades.

Background: KCNA6 encodes the voltage-gated potassium channel Kv1.6, a subunit involved in regulating neuronal excitability and action potential repolarization. Previous clinical case reports have demonstrated that KCNA6 mutations affecting potassium channel function correlate with a range of early infantile epileptic and neurodevelopmental disorder phenotypes. This report aims to document the condition of a novel mutation Kv1.6 p.Leu448Val in another patient exhibiting similar clinical features. Patient’s asymptomatic father did not carry the variant while mother’s DNA was not available.

Methods: Target mutant mRNA was obtained through site-directed mutagenesis, introduced into Xenopus laevis oocytes for expression, and its electrophysiological functional characteristics were assessed using the two-electrode voltage clamp technique. Wild-type and mutant RNA were also co-injected in 1:1 ratio. Results： This patient presented with febrile seizures before the age of one, accompanied by phenotypic features including global developmental delay, absent speech, and autism. The p.Leu448Val mutation is located within the S6 α-helical region, overlapping with previously reported mutations at the channel gate. Functional characterisation conducted in Xenopus oocytes revealed that the mutation disrupts the normal closure mechanism, resulting in increased potassium currents. These gain-of-function effects persisted when p.Leu448Val was co-injected with wild-type subunits.

Discussion: The clinical presentation of this individual and the electrophysiological features of the p.Leu448Val channel were consistent with the previously reported cases of KCNA6-associated epilepsy, confirming the pathogenicity of this variant. This case expands the clinical and genetic spectrum, and further establishes the causative role, of KCNA6 gain -of -function variants in developmental and epileptic encephalopathies .