【摘要】 目的 报道3个与DEPDC5基因相关的癫痫家系，并分析其临床及遗传学特征。方法 收集3例患儿临床资料，提取患儿及其父母外周血DNA,采用高通量全外显子测序方法检测致病基因，采用Sanger法对变异位点进行验证，最后结合临床确定突变位点的致病性。结果 3例患儿起病中位年龄为3.4岁，临床表现为不同形式的癫痫发作，包括失神发作、局灶性发作及全面强直-阵挛发作。A患儿存在脑结构异常，其母亲有癫痫家族史。C患儿合并有注意缺陷多动障碍。3例患儿中有2例经2种抗癫痫药物联合治疗后控制不佳，1例已停药1 a,无发作。3例患儿行基因检测后均发现DEPDC5基因新发致病性突变位点，通过Sanger法验证后结合蛋白质预测软件分析结果可明确其致病性。结论 根据临床表现、家族史、头颅影像学、脑电图结果及基因检测可明确3例DEPDC5基因相关癫痫患儿的诊断。DEPDC5基因相关癫痫患儿临床表现异质性高，癫痫发作形式不一，可合并脑结构异常及神经精神障碍等，发展为药物难治性癫痫的可能性大。本研究证实了3个DEPDC5基因新突变位点，丰富了DEPDC5基因突变谱。更多还原

【Abstract】 Objective To report three families with epilepsy related to DEPDC5 gene and analyze their clinical and genetic characteristics.Methods The clinical data of three children were collected, the peripheral blood DNA of the children and their parents were extracted, the pathogenic genes were detected by high-throughput full exon sequencing, the mutation sites were verified by Sanger method, and finally the pathogenicity of the mutation sites was determined according to the clinic.Results The median age of onset of 3 children was 3.4 years old, and the clinical manifestations were different forms of seizures, including absence seizures, focal seizures and generalized tonic clonic seizures. Child A had abnormal brain structure, and her mother had a family history of epilepsy. Child C had attention deficit hyperactivity disorder. Two of the three children had poor control after combined treatment with two antiepileptic drugs and one had stopped taking the drug for one year, with seizure free. New pathogenic mutation sites of DEPDC5 gene were found after gene detection of three children, and the pathogenicity of DEPDC5 gene can be confirmed by Sanger method and protein prediction software analysis results.Conclusion According to clinical manifestations, family history, cranial imaging, EEG results and gene detection, the diagnosis of three children with DEPDC5 gene related epilepsy can be determined. Children with epilepsy associated with DEPDC5 gene have high heterogeneity in clinical manifestation, different seizure forms, brain structural abnormalities and neuropsychiatric disorders. It is more likely to develop into drug-resistant epilepsy. This study confirmed three new mutation sites of DEPDC5 gene and enriched the mutation spectrum of DEPDC5 gene.更多还原