SETD1B variants associated with absence seizures

Abstract

Aim

Exploring the association between SETD1B variants and absence seizures (ASs).

Methods

We engaged a small cohort of four pediatric epilepsy patients with identified SETD1B variants and conducted a comprehensive review of 50 documented instances. Clinical profiles were meticulously compiled, and genetic screening was executed via trio-based whole-exome sequencing. Our literature survey centered on AS manifestations linked to SETD1B alterations, utilizing descriptive statistics for analysis.

Results

The quartet of new cases presented with developmental impediments, cognitive deficits, and epileptic manifestations. Pathogenicity was established in the detected SETD1B variants. Among the 54 individuals, 26 (accounting for 48.1 %) presented with AS during the course of the disease. The median seizure onset age stood at 44.8 months, with a majority displaying cognitive challenges and autistic traits. Anti-epileptic drug therapies proved efficacious in 70.8 % of the instances. Notably, variants within the N-SET, SET, and post-SET domains of SETD1B were prevalent in 46.2 % of the AS-afflicted cohort.

Discussion

Our findings accentuate the potential influence of SETD1B variants in AS pathogenesis, these variants may perturb neuronal excitability, possibly via modulation of histone methylation landscapes. The insights garnered here deepen our grasp of AS's genetic architecture.

Conclusion

Our study identified four novel SETD1B variants, highlighting that the importance of AS as part of the phenotype among individuals with SETD1B, demonstrated by 3 novel cases, and supported by review of the literature. Our findings also suggest that the SET domains may play a potential role in the pathogenesis of AS, providing a clue for future mechanistic research.