Epilepsja związana z mutacjami genu CSNK2B: opis rodziny i przegląd piśmiennictwa

BACKGROUND: CSNK2B mutations are associated with Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), in which epilepsy is a common clinical feature. To describe the epilepsy phenotype of CSNK2B mutations, we reported a family with a novel CSNK2B mutation, added this information to the existing literature, and then combined these data for analysis to offer some observations. METHODS: We performed trio-based whole-exome sequencing and Sanger validation in a family with early-onset seizures. In addition, we reviewed published reports of patients carrying pathogenic or likely pathogenic CSNK2B mutations, extracted epilepsy phenotypic data, and analyzed the correlation of epilepsy severity with the mutation type and the mutation location within the protein (specific amino acid position or domain). RESULTS: We identified a novel pathogenic nonsense mutation in CSNK2B, c.240T > G, p. Tyr80*, among three affected members of one family. Together with published cases, a total of 103 individuals with sufficient epilepsy-related data were available for analysis. Seizures occurred in 94.2% of patients, 87.4% were diagnosed with epilepsy, and seizure onset before 24 months of age in 87.2%. There were no significant differences in the incidence of seizures, epilepsy, and drug‑resistant epilepsy (DRE) among different mutation type groups (P = 0.313, 0.069, and 0.690, respectively). Subgroup analysis of missense mutations into conservative and radical substitutions also revealed no significant differences in epilepsy and DRE incidence (P = 1.000 and P = 0.714, respectively). In contrast, mutation location appeared to be more informative: mutations outside annotated protein domains showed higher epilepsy penetrance than those within domains (P = 0.034). Exploratory analyses also suggested that the distribution of mutations across different domains varies, which may affect epilepsy severity, though further validations are required. CONCLUSIONS: This study expanded the mutational and phenotypic spectrum of CSNK2B-related disorders by identifying a novel pathogenic nonsense mutation. Protein-level mutation location appeared to be more informative than mutation type in relation to epilepsy severity. We noticed that the composition of intradomain mutations may play a part in predicting DRE susceptibility. Further large-scale validation studies are in need.