目的探讨CHD2基因相关的癫■性脑病发病年龄与基因型关联性特点,提高CHD2致病变异可致早期癫■性脑病的临床认识。方法对复旦大学附属儿科医院收治的1例新生儿癫■性脑病患儿进行临床表型及基因型分析。以"CHD2基因"为关键词...目的探讨CHD2基因相关的癫■性脑病发病年龄与基因型关联性特点,提高CHD2致病变异可致早期癫■性脑病的临床认识。方法对复旦大学附属儿科医院收治的1例新生儿癫■性脑病患儿进行临床表型及基因型分析。以"CHD2基因"为关键词,检索中国知网、维普数据库和万方数据库,以"CHD2"为基因名称检索HGMD数据库,并以"CHD2gene"为关键词检索PubMed、Web of Science数据库,检索时间为建库至2018年11月29日,总结CHD2缺陷致癫■性脑病的临床特征及遗传学特点。结果患儿男,在新生儿期表现为惊厥发作、肌张力异常及喂养困难,全外显子测序分析提示CHD2基因存在新发可能致病变异[NM_001271:exon31:c.3951G>C(p.L1317F)]。文献检索目前国内外已报道CHD2基因致病病例67例,均尚未见新生儿期出现明显神经系统异常表现,但61.1%(11/18)病例存在癫■起病前神经发育障碍的病史。结合已报道病例及本文病例,癫■首次发作年龄为6个月以内(含6个月)共3例,均为错义突变;首次发作年龄6个月以上19例,其中5例为错义突变(26.3%)。结论 CHD2基因缺陷致癫■性脑病可在新生儿期即出现惊厥发作。CHD2基因的错义变异可能有引起癫■早期发作的倾向。仅表现为神经发育障碍,而无癫■发作的患儿,也应考虑可能携带CHD2致病变异的可能性。展开更多
Importance:CHD2 is a member of the chromodomain helicase DNA-binding(CHD)family of proteins,which have important roles in the regulation of gene expression.Dysregulation of this protein may lead to various disorders.O...Importance:CHD2 is a member of the chromodomain helicase DNA-binding(CHD)family of proteins,which have important roles in the regulation of gene expression.Dysregulation of this protein may lead to various disorders.Objective:To delineate the genotypes and phenotypes of CHD2-related epilepsy.Methods:We analyzed the medical history,magnetic resonance imaging findings,and video-electroencephalogram recordings of 17 patients withCHD2 mutations in the Neurology Department of Beijing Children’s Hospital from June 2016 to June 2021.Results:Age at seizure onset ranged from 6 months to 10 years;the median age at onset was 4 years.Generalized tonic-clonic,myoclonic,eyelid myoclonic,atonic,atypical absence,myoclonic-atonic,and spasm seizures were observed.Ten of the 17 patients had multiple types of seizures.One patient exhibited photosensitivity epilepsy and one patient exhibited grid image-induced visual reflex epilepsy.Developmental disability was present in 14 patients,while autism features were present in five patients.Sixteen patients hadde novo mutations ofCHD2;one patient had an inherited variant.Eleven mutations were novel.One patient had two mutations;that patient exhibited development delay and refractory epilepsy.Seizures were controlled in eight patients,improved in seven patients,and resistant to treatment in two patients.Interpretation:Phenotype severity in patients withCHD2 variants ranged from drug-responsive seizures to severe epileptic encephalopathy.Most patients exhibited developmental disorders.展开更多
文摘目的探讨CHD2基因相关的癫■性脑病发病年龄与基因型关联性特点,提高CHD2致病变异可致早期癫■性脑病的临床认识。方法对复旦大学附属儿科医院收治的1例新生儿癫■性脑病患儿进行临床表型及基因型分析。以"CHD2基因"为关键词,检索中国知网、维普数据库和万方数据库,以"CHD2"为基因名称检索HGMD数据库,并以"CHD2gene"为关键词检索PubMed、Web of Science数据库,检索时间为建库至2018年11月29日,总结CHD2缺陷致癫■性脑病的临床特征及遗传学特点。结果患儿男,在新生儿期表现为惊厥发作、肌张力异常及喂养困难,全外显子测序分析提示CHD2基因存在新发可能致病变异[NM_001271:exon31:c.3951G>C(p.L1317F)]。文献检索目前国内外已报道CHD2基因致病病例67例,均尚未见新生儿期出现明显神经系统异常表现,但61.1%(11/18)病例存在癫■起病前神经发育障碍的病史。结合已报道病例及本文病例,癫■首次发作年龄为6个月以内(含6个月)共3例,均为错义突变;首次发作年龄6个月以上19例,其中5例为错义突变(26.3%)。结论 CHD2基因缺陷致癫■性脑病可在新生儿期即出现惊厥发作。CHD2基因的错义变异可能有引起癫■早期发作的倾向。仅表现为神经发育障碍,而无癫■发作的患儿,也应考虑可能携带CHD2致病变异的可能性。
基金National Natural Science Foundation of China(Grant/Award Number:81301118)。
文摘Importance:CHD2 is a member of the chromodomain helicase DNA-binding(CHD)family of proteins,which have important roles in the regulation of gene expression.Dysregulation of this protein may lead to various disorders.Objective:To delineate the genotypes and phenotypes of CHD2-related epilepsy.Methods:We analyzed the medical history,magnetic resonance imaging findings,and video-electroencephalogram recordings of 17 patients withCHD2 mutations in the Neurology Department of Beijing Children’s Hospital from June 2016 to June 2021.Results:Age at seizure onset ranged from 6 months to 10 years;the median age at onset was 4 years.Generalized tonic-clonic,myoclonic,eyelid myoclonic,atonic,atypical absence,myoclonic-atonic,and spasm seizures were observed.Ten of the 17 patients had multiple types of seizures.One patient exhibited photosensitivity epilepsy and one patient exhibited grid image-induced visual reflex epilepsy.Developmental disability was present in 14 patients,while autism features were present in five patients.Sixteen patients hadde novo mutations ofCHD2;one patient had an inherited variant.Eleven mutations were novel.One patient had two mutations;that patient exhibited development delay and refractory epilepsy.Seizures were controlled in eight patients,improved in seven patients,and resistant to treatment in two patients.Interpretation:Phenotype severity in patients withCHD2 variants ranged from drug-responsive seizures to severe epileptic encephalopathy.Most patients exhibited developmental disorders.
