Background: Paucity of data from India on functional alterations (funotypes) of ion channels
in DEE and relation between funotype–phenotype correlations in defining the pathogenic
potential of gene phenotypic expressions and their relationship to the molecular mechanisms
of the genes.
Hypothesis and Aims: There is association between the functional changes in ion channel genes and their
corresponding phenotypes A distinct funotype or funotype–phenotype correlation helps
in defining the pathogenic potential of a gene. Studying these functional changes
in mutants would help in better understanding of the mechanisms of epilepsy and providing
targeted treatment.
Methodology: An observational hospital-based study was undertaken on subjects with DEE <18 years,
whose families consented and underwent genetic testing during a study period of 2016
to 2022 by next-generation sequencing (NGS) or multiplex ligand protein amplification.
Yield was considered based on demonstration of pathogenic/likely pathogenic variants
only and variants of unknown significance (VUS) were documented. We plan to include
potential epilepsy-associated ion channel genes and find the function of these variants
using in silico tools.
Expected Outcomes and Conclusion: Funotype should be an essential consideration in evaluating the pathogenicity of
especially de novo mutations. Epilepsy-associated ion channel genes provide insights
into the underlying mechanisms of epileptogenesis, help to identify novel treatment,
provide precision treatment, and guide prognosis.
