Odkrycie nowej jednoallelicznej mutacji w genie SCN1B u rodzin spokrewnionych z wczesnym początkiem padaczki: opis przypadków i przegląd piśmiennictwa

BACKGROUND: Pathogenic variants in SCN1B, the gene encoding the sodium channel β1 subunit, are associated with generalized epilepsy with febrile seizures plus (GEFS+) and related epilepsy disorders. These disorders exhibit phenotypic heterogeneity and varying clinical severity under autosomal dominant as well as recessive inheritance models. The current study investigated the genetic basis of epilepsy in two consanguineous Pakistani families. METHODS: We investigated two unrelated Pakistani families with four affected individuals presenting with early-onset epilepsy. Exome sequencing (ES) was performed in the index cases in both families to identify the underlying genetic cause. Sanger sequencing was used for validation and segregation analysis in additional family members. RESULTS: The affected individuals presented overlapping clinical features including early-onset drug-refractory seizures, developmental delay, intellectual disability, and autism spectrum disorder. ES identified a novel homozygous canonical splice-site variant in SCN1B (NM_001037.5): c.591-2A>G p.(?) in all affected individuals. CONCLUSIONS: A novel homozygous SCN1B splice site variant was identified in two unrelated consanguineous families as the most likely cause of the early-onset epilepsy. These findings underscore the importance of genetic screening and tailored therapeutic strategies in epilepsy management.