与失神发作相关的SETD1B变异

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology Pub Date : 2025-01-01 DOI:10.1016/j.ejpn.2024.12.002

Genfu Zhang , Yue Niu , Zhao Xu , Jiong Qin , Zhixian Yang

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引用次数: 0

摘要

目的探讨SETD1B变异与癫痫缺失（ASs）之间的关系。方法：研究人员招募了4名患有SETD1B变异的儿童癫痫患者，并对50例记录在案的病例进行了全面回顾。精心编制临床资料，并通过基于三组的全外显子组测序进行遗传筛选。我们的文献调查集中于与SETD1B改变相关的AS表现，利用描述性统计进行分析。结果4例新发病例均有发育障碍、认知障碍和癫痫表现。在检测到的SETD1B变异中建立了致病性。54例患者中，26例（占48.1%）在病程中出现AS。癫痫发作的中位年龄为44.8个月，大多数患者表现出认知障碍和自闭症特征。抗癫痫药物治疗有效率为70.8%。值得注意的是，在46.2%的as患者中，SETD1B的N-SET、SET和后SET结构域内的变异普遍存在。我们的研究结果强调了SETD1B变异在AS发病机制中的潜在影响，这些变异可能通过调节组蛋白甲基化景观来扰乱神经元的兴奋性。在这里获得的见解加深了我们对AS基因结构的把握。我们的研究发现了4个新的SETD1B变异，突出了AS作为SETD1B个体表型的一部分的重要性，3个新病例证明了这一点，并得到了文献综述的支持。我们的发现也提示SET结构域可能在AS的发病机制中发挥潜在的作用，为未来的机制研究提供了线索。

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SETD1B variants associated with absence seizures

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.

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来源期刊

European Journal of Paediatric Neurology 医学-临床神经学

CiteScore

6.30

自引率

3.20%

发文量

115

审稿时长

81 days

期刊介绍： The European Journal of Paediatric Neurology is the Official Journal of the European Paediatric Neurology Society, successor to the long-established European Federation of Child Neurology Societies. Under the guidance of a prestigious International editorial board, this multi-disciplinary journal publishes exciting clinical and experimental research in this rapidly expanding field. High quality papers written by leading experts encompass all the major diseases including epilepsy, movement disorders, neuromuscular disorders, neurodegenerative disorders and intellectual disability. Other exciting highlights include articles on brain imaging and neonatal neurology, and the publication of regularly updated tables relating to the main groups of disorders.