关键词: CSNK2B基因, 全外显子组家系测序, Poirier-Bienvenu神经发育综合征, 早发性癫痫

Abstract:

Objective To analyze the gene mutation of a child with early-onset seizures by trio-whole-exome sequencing（Trio-WES），and to investigate the pathogenic factors of Poirier-Bienvenu neurodevelopmental syndrome（POBINDS）. Methods The clinical data of a child with early-onset seizures were collected，Trio-WES was performed on the child and his parents，and the mutation sites were verified by Sanger sequencing. The hazards of mutation sites were assessed by bioinformatics analysis. Results The child exhibited recurrent myoclonic seizures at the age of 3 months. Although the frequency of seizures was decreased after treatment with sodium valproate，it was still uncontrollable. Trio-WES results indicated that the child had a missense mutation [c.560T>G（p.Leu187Arg）] in CSNK2B gene. The mutation sites of his parents were wild-type，which was a de novo mutation site. According to the results of genetic analysis and clinical symptoms，the child was definitely diagnosed as POBINDS. A search of public SNP databases（ESP database，1000 Genomes database and ExAC database） did not find that the mutation site was included. Sanger sequencing confirmed the existence of mutation site. The results of protein structure simulation analysis showed that the c.560T>G（p.Leu187Arg） may lead to a decreasing in the stability of casein kinase 2（CK2） tetramer structure，thereby affecting its biological function. Conclusions POBINDS caused by CSNK2B gene mutation may be the pathogenic factor of recurrent myoclonic seizures in children，suggesting that the possibility of POBINDS should be considered in the clinical treatment of early-onset seizures.

Key words: CSNK2B gene, Trio-whole-exome sequencing, Poirier-Bienvenu neurodevelopmental syndrome, Early-onset seizure