Badanie wariantów genetycznych białka zawierającego domenę bromodomeny 2 (BRD2) w padaczce mioklonicznej młodzieżowej (JME): Wnioski z analizy genetycznej i wzbogacenia genów
Exploring human bromodomain-containing protein 2 (BRD2) genetic variants in juvenile myoclonic epilepsy (JME): Insights from genetic and gene enrichment analysis
W skrócie
[Preprint - wstępne wyniki] Naukowcy przeanalizowali mutacje w genie BRD2 u 55 pacjentów z padaczką miokloniczną młodzieżową i znaleźli zmiany genetyczne u 39 z nich. Badania wykazały, że warianty tego genu mogą wpływać na podatność na tę formę padaczki poprzez zaburzenia w procesach regulacji DNA i transkrypcji. Odkrycia te mogą pomóc w opracowaniu nowych sposobów leczenia padaczki mioklonicznej u młodzieży.
Oryginalny abstract (angielski)
Abstract Purpose: Juvenile myoclonic epilepsy (JME) is a common subtype of genetic generalized epilepsy characterized by myoclonic jerks, generalized tonic–clonic seizures, and occasional absence seizures. Although several susceptibility genes have been implicated in JME, the contribution of coding variants within the bromodomain-containing protein 2 (BRD2) gene remain inadequately understood . This study investigates genetic variants within exon 13 of the Bromodomain Containing Protein-2 (BRD2) gene in juvenile myoclonic epilepsy (JME) patients. Methods: A cohort of 55 JME patients and 55 healthy controls was analysed using Sanger sequencing. Mutational changes in the BRD2 gene were identified in 39 JME participants, with sequence data deposited under GenBank accession numbers KX173310 to KX173324. Demographic analysis revealed JME prevalence in adolescents and children. In silico analysis identified single nucleotide polymorphisms (SNPs), while gene enrichment and protein-protein interaction (PPI) networks evaluated BRD2's functional role. Results: Mutational changes were detected in 39 JME patients, and the corresponding sequences were deposited in GenBank (KX173308 - KX173324). In silico analysis revealed recurrent SNPs, including G>A at position 3947, C>T at position 4092, and G>A at position 4107 (relative to reference sequences). Gene enrichment and PPI analysis underscored BRD2's involvement in chromatin remodelling, DNA replication, and transcriptional regulation. Additionally, BRD2 was associated with pathways linked to cancer, highlighting its therapeutic potential. Significance: The findings highlight the potential contribution of BRD2 exon 13 variants to JME susceptibility and emphasize the importance of BRD2-mediated regulatory pathways in epilepsy pathogenesis. These results provide a foundation for future functional studies and may facilitate the development of targeted therapeutic strategies in JME.