Warianty genetyczne związane z ogniskową epilepsją i ich związek z arytmiami serca oraz zaburzeniami rozwojowymi

PURPOSE: variants have been identified in cardiac arrhythmias and developmental disorders (DD). Here, we aimed to explore the association between and epilepsy and the mechanism underlying phenotypic heterogeneity. METHODS: Trio-based whole-exome sequencing was performed in patients with focal epilepsy. Genes with recurrently identified variants were selected for further studies. RESULTS: Three variants were identified in three patients with focal epilepsy. All variants presented no minor allele frequency in the Genome Aggregation Database, which was significantly lower than that of benign variants in the ClinVar database. The three variants were evaluated as pathogenic or likely pathogenic variants according to the updated American College of Medical Genetics and Genomics (ACMG) classification. Two patients experienced infrequent seizures and became seizure free. The other patient had refractory epilepsy with DD and arrhythmia. Previously, 138 variants were reported to be associated with arrhythmias, of which 39 were classified as pathogenic or likely pathogenic; 30 variants were associated with DD, 19 of which were classified as pathogenic or likely pathogenic according to the updated ACMG classification. Further analysis indicated that null variants were more common in DD than in epilepsy (p=1.39×10) and arrhythmias (p=6.31×10). The epilepsy-associated variants were predominantly located in the voltage sensor region (p=9.03×10), whereas the arrhythmia-associated variants were mostly located in the linker region (p=2.13×10). There was a greater percentage of variants in patients with epilepsy and DD than in those with arrhythmias (p=6.02×10; p=2.47×10). CONCLUSION: is potentially a candidate causative gene of focal epilepsy. The genotype-phenotype correlation of helps explain phenotypic heterogeneity.