60例不明原因早期癫癎性脑病临床特点及全基因组拷贝数变异分析

目的 研究不明原因早期癫癎性脑病(EEEs)患儿临床特点,并进行全基因组拷贝数变异检测,寻找致病性微缺失/重复.方法 收集2012 年7 月至2013 年4 月60 例不明原因EEEs 患儿临床资料进行分析,采集患儿及其父母样本,应用SNP array 技术对患儿进行全基因组拷贝数变异检测,结合荧光原位杂交技术进行验证及父母来源分析,寻找可疑致病性拷贝数变异.结果 60 例不明原因EEEs 患儿诊断婴儿痉挛症34 例,大田原综合征3 例,婴儿严重肌阵挛性癫癎3 例,余20 例分型不明确.77% 患儿伴有中重度智力障碍.颅脑影像学检查提示35% 患儿脑发育不良或脑萎缩.54 例患儿中,17% 有小头畸形.经治疗28 例患儿癫癎控制,16例未控制,5 例死亡,1 例失访.全基因组拷贝数变异分析结果:5 人发现7 个致病性或可疑致病性拷贝数变异.结论 不明原因EEEs 临床表现多样,预后差.全基因组拷贝数变异分析可发现致病性或可疑致病性拷贝数变异,丰富癫癎脑病基因型数据库,促进对不明原因EEEs 病因学的进一步认识,为患者家庭再生育的遗传咨询提供理论依据.

Clinical features and genome-wide copy number variation analysis in 60 children with early-onset epileptic encephalopathies of unknown cause

Objective To study the clinical features of early-onset epileptic encephalopathies (EEEs) of unknowncause, and to identify pathogenic microdeletion/microduplication of EEEs by genome-wide analysis of copy numbervariations (CNVs). Methods The clinical data of 60 children diagnosed with unexplained EEEs between July 2012 and April 2013 were obtained and analyzed. Specimens were collected from the selected children and their parents.Single nucleotide polymorphism array was used to detect genome-wide CNVs, and fluorescence in situ hybridizationwas performed to verify the results and analyze the source of the parents, further to identify suspected pathogenic CNVsof EEEs. Results Among the 60 children with unexplained EEEs, 34 were diagnosed with West syndrome, 3 withOhtahara syndrome, 3 with Dravet syndrome, and 20 with unclassified EEEs. In total, 77% of the patients were associatedwith moderate to severe mental retardation. Head imaging test implied that 35% of the patients had brain dysplasiaor astrophy. Among 54 patients, 17% showed microcephalus. After treatment, 28 patients had clinical seizures undercontrol, 16 out of control, 5 dead, and 1 lost to follow-up. Genome-wide analysis of CNVs showed that 7 pathogenic orsuspected pathogenic CNVs were present in 5 patients. Conclusions EEEs of unknown cause are associated with highphenotypic heterogeneity and poor prognosis. Genome-wide CNVs analysis can demonstrate pathogenic or suspectedpathogenic CNVs. This research expands the gene bank of EEEs and improves the understanding about possible etiologyof unexplained EEEs. The results provide a reference for genetic counseling regarding reproduction in the patient''sfamily.