一例早发癫痫性脑病42型患儿的临床表型及基因变异分析

Clinical manifestation and genetic analysis of a child with early infantile epileptic encephalopathy 42

目的探讨一例早发癫痫性脑病42型患儿的基因型与表型特征。方法详细询问患儿的病史,结合其临床表型、影像学及遗传学特征进行临床诊断,并对其父母进行Sanger测序验证,明确致病变异的来源。结果患儿无意识头向一侧轻度歪斜,眼球向同侧斜视,脑电图异常放电。磁共振成像显示左额后皮层可疑异常信号,伴右侧上颌窦及筛窦炎症。全外显子组测序提示患儿携带CACNA1A基因c.5789G>A杂合变异,Sanger测序提示父母双方并未携带相同的变异,提示其为新发变异。结论先证者CACNA1A基因c.5789G>A杂合变异可能是导致其早发癫痫性脑病42型的原因。

Objective To analyze the clinical phenotype and genetic characterization of a child with early infantile epileptic encephalopathy.Methods The proband was subjected to history taking diagnosed based on clinical manifestation,magnetic resonance imaging and whole exome sequencing.Sanger sequencing was carried out to determine the origin of the pathogenic variant.Results The proband unconsciously tilts his head to one side with squint.Electroencephalogram revealed abnormal discharge.MRI indicated suspicious abnormal signal shadow in the left posterior frontal cortex in addition with inflammation signs in the right maxillary sinus and ethmoid sinus.Whole exome sequencing(WES)revealed that the proband has carried heterozygous c.5789G>A mutation in the CACNAIA gene.The results of Sanger sequencing were in keeping with that of WES.Neither parents of the proband carried the same mutation.Conclusion The heterozygous c.5789G>A mutation of the CACNAIA gene probably underlay the early infantile epileptic encephalopathy 42 in the proband and was de novoin origin.