NR4A2基因变异所致的发育性癫痫性脑病1例并文献复习

One case of developmental epileptic encephalopathy caused by NR4A2 gene variation and literature review

目的分析1例NR4A2基因变异所致的发育性癫痫性脑病患儿的临床特点,总结该类疾病的临床表型及基因型,以提高临床医师对该类疾病的认识。方法收集2022年8月就诊于临沂市人民医院的1例儿童发育性癫痫性脑病患儿的临床资料,完善视频脑电图、颅脑磁共振成像及家系全外显子测序,再对可疑突变位点采用Sanger测序进行验证。查阅相关文献,总结NR4A2基因所致神经系统疾病的临床表型及遗传学特点。结果发现患儿在NR4A2基因c.866G>A(p.A289H)位点存在1个杂合错义突变,为新发变异,父母均为野生型。根据美国医学遗传学与基因组学学会变异分级评定为疑似致病性变异。经查阅文献发现目前国际上共有16例相关病例报道,均存在不同程度的精神发育迟缓/智力低下,还有语言障碍、癫痫发作、肌张力改变及不同心理行为问题。结论NR4A2基因不仅与多巴反应障碍性疾病相关,还与神经发育、智力障碍及语言发育迟缓、癫痫相关;位点c.866G>A(p.A289H)的检出扩大了NR4A2的基因谱,并提出NR4A2基因是发育性癫痫性脑病的致病基因之一。

Objective To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation,and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease.Methods The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected,video electroencephalogram,craniocerebral magnetic resonance imaging and family whole exon sequencing were improved,and the suspected mutation sites were verified by Sanger sequencing.Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene.Results It was found that there was a heterozygous missense mutation at the locus c.866G>A(p.A289H)of NR4A2 gene in the child,which was a de novo mutation,and both parents were wild type.According to the American Society of Medical Genetics and Genomics variation classification,it was assessed as a suspected pathogenic variation.Through literature review,there were 16 related cases reported internationally,with clinical phenotypes including mental retardation/mental retardation,language disorders,seizures,muscle tone changes and different psychological and behavioral problems.Conclusions The NR4A2 gene is not only associated with dopa responsive disorders,but also with neurological development,intellectual impairment,language development delay,and epilepsy.The mutation of NR42A gene c.866G>A(p.A289H)is the genetic cause of the patient,and the detection of this locus expands the NR4A2 gene spectrum.NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.