Sub-molecular Mechanism of Genetic Epilepsy

Protein is the essential functional molecule in living organisms. A protein is featured by finely structured domains, which are encoded by genetic sequences. Mutations in a gene potentially result in functional alteration of the protein and thus cause diseases. From the perspective of molecular structure, different domains of a protein play distinct roles. Mutations of different locations are thus potentially associated with various damaging effects and subsequently lead to phenotypical variation. Similarly, the bio-physical feature of the substituted amino acids caused by mutations is also a determinant of the damaging effect. Such submolecular implication would be a critical factor in considering the pathogenicity of mutations and determining the gene-disease association, especially for neurogenetic diseases like epilepsy that revealed major phenotypical heterogeneity.

So far, more than 4000 genes have been associated with human diseases (https://omim.org/). A gene could be associated with a distinct phenotype, but in majority circumstances, it is associated with a spectrum of phenotypes that varied in severity or other aspects, for which the underlying mechanism is mostly unknown. Previously, sub-molecular implications have been demonstrated to be a determinant of phenotypical variation in several molecules, such as sodium channel Nav1.1, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (14-3-3γ), and disheveled Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5). Further studies are advocated to disclose the submolecular mechanism of genetic diseases, such as genetic epilepsy, setting a submolecular stage of medicine.

This Research Topic aims to collect research contributions on unraveling the submolecular mechanism of genetic epilepsy. We welcome original research and review articles covering, but not limited to, the following themes:
1. Molecular sub-regional implication of mutations in the phenotypical variation of genetic epilepsy.
2. Relationships between the substituted amino acid in residual and functional alteration or phenotypical variation of genetic epilepsy.
3. Correlations between genetic impairment (or functional alteration) and phenotypical variation of genetic epilepsy.
4. Isoform-associated phenotype of phenotypical variation of genetic epilepsy.
5. Studies on other aspects of genotype-phenotype correlation of genetic epilepsy.
6. Identifying novel candidate genes associated with epilepsy with analysis on the molecular or submolecular effect of mutations.

This would be adding new thoughts of genetic epilepsy research. We hope that you will find it of interest and join us in creating a new era of medicine.