一例ARHGEF9基因同义变异相关的早发性婴儿癫痫脑病的临床分析

Clinical analysis of early-onset infantile epileptic encephalopathy associated with synonymous variant of the ARHGEF9 gene

目的探讨ARHGEF9基因同义变异导致早发性婴儿癫痫脑病8型的临床特点。方法对一例癫痫伴有全面性发育迟缓的患儿的临床资料进行总结,并采集外周血样行家系全外显子组测序。结果该患儿以智力发育迟缓、癫痫发作,且表现出明显的多动、冲动以及声音过敏等相对特异的表现。全外显子组测序发现其携带ARHGEF9基因新发同义变异c.741C>T(p.Cys247Cys),RNA剪接实验结果表明该变异可导致异常剪接,第5外显子缺失55 bp。结论发现了ARHGEF9的新发的同义变异,经RNA逆转录实验证实可影响Collybistin蛋白的合成,导致相应的临床症状。ARHGEF9基因变异与男性儿童早发性癫痫脑病密切相关,同时可以伴听觉过敏、多动冲动等相对特异的表型。本研究丰富了ARHGEF9基因致病的变异谱及相关的临床表型。

Objective To explore the clinical characteristics of a child with early-onset infantile epileptic encephalopathy type 8 associated with synonymous variant of ARHGEF9 gene.Methods Clinical data of the patient was summarized.The child and his parents were subjected to trio-whole exome sequencing.Results The child has presented with global developmental delay,epilepsy,impulsive behavior,hypersensitivity to sound,and mental retardation.He was found to harbor a de novo synonymous variant c.741C>T(p.Cys247Cys)of the ARHGEF9 gene.RNA splicing analysis confirmed that the variant has led to abnormal splicing of exon 5,resulting in a 55-bp deletion.Conclusion The clinical features of ARHGEF9 gene-related early-onset infantile epileptic encephalopathy type 8 includes mental and motor developmental delay,epilepsy,auditory allergy,and hyperactivity impulsivity.For synonymous variant,in vitro study and transcriptional experiment may be carried out to evaluate its functional and splicing effect.Above finding has enriched the phenotypic and genotypic spectrum of the ARHGEF9 gene.