MECP2基因突变表型特点四例  

Phenotypic characteristics of four cases with mutations in the MECP2 gene

作　　者：赵倩 赵昕 李保驰 吴文娟 李宝广[1] Zhao Qian;Zhao Xin;Li Baochi;Wu Wenjuan;Li Baoguang(Department of Neurology,Children's Hospital of Hebei Province,Shijiazhuang 050031,China)

机构地区：[1]河北省儿童医院神经内科,石家庄050031 [2]河北省儿童医院呼吸科

出　　处：《脑与神经疾病杂志》2024年第11期675-682,共8页Journal of Brain and Nervous Diseases

基　　金：河北省政府资助临床医学人才培养项目(ZF2021028)。

摘　　要：目的总结4例MECP2基因突变患儿的表型特点。方法选取河北省儿童医院神经内科2019年8月至2024年4月收治的MECP2基因突变患儿及父母外周血DNA,采用高通量测序技术进行外显子组基因检测。总结4例MECP2基因突变患儿的病历数据,同时结合文献进行遗传学结果分析。结果收集4例患儿,男性2例,女性2例,中位起病年龄1岁10个月,3例患儿有发育障碍,3例患儿MRI显示脑外间隙增宽,4例患儿有癫痫发作并服用抗癫痫药物治疗,2例患儿诊断Rett综合征。2例母源变异,例1基因型c.343C>T(p.Arg115Cys),例2基因型c.925C>T(p.Arg309Trp),均为男性、错义突变;2例为自发突变,例3基因型c.880C>T(p.Arg294Ter),例4基因型c.763C>T(p.Arg255Ter),均为女性、无义突变。结论(1)基因检测可早期初步评估患儿的病情严重程度及预后;(2)MECP2基因突变患儿脑部异常放电可能多以Rolandic区为主;(3)2例男性患儿致病基因来源于无临床症状的母亲,其母亲无症状可能是由于X染色体非随机失活和突变MECP2等位基因的优先失活所致;(4)本组Rett综合征合并癫痫患儿服用左乙拉西坦、丙戊酸钠后病情可控制;(5)通过对4例MECP2基因突变临床表型及遗传学分析,丰富了MECP2基因突变临床表型谱,加强了MECP2基因突变基因型与表型之间的联系。Objective To summarize the phenotypic characteristics of 4 children with MECP2 gene mutation.Methods Children with MECP2 gene mutation and their parents'peripheral blood DNA admitted to the Department of Neurology of Hebei Provincial Children's Hospital from August 2019 to April 2024 were selected for exome gene detection using high-throughput sequencing technology.The case data of the four children with MECP2gene mutation were summarised,and the genetic results were analyzed in conjunction with the reviewed literature.Results Four children were collected,2 males and 2 females,with a median age of onset of 1 year and 10 months;3 had developmental disorders,three had widened extracerebral gaps on MRI,4 had seizures and were treated with antiepileptic medication,and 2 had a diagnosis of Rett syndrome.Two cases of maternal variant,case 1 with genotype c.343C>T(p.Arg115Cys),case 2 with genotype c.925C>T(p.Arg309Trp),both male,missense mutations;2 cases were spontaneous mutations,case 3 genotype c.880C>T(p.Arg294Ter),case 4 genotype c.763C>T(p.Arg255Ter),both female,nonsense mutations.Conclusion(1)Genetic testing can be used for early and preliminary assessment of the severity of the disease and prognosis of the children;(2)Abnormal discharges in the brain of children with mutations in the MECP2 gene may be predominantly in the Rolandic region;(3)The causative genes of the two cases of male children originated from their asymptomatic mothers,and the asymptomatic mothers of these cases were probably due to the non-random deactivation of the X-chromosome and preferential deactivation of mutant MECP2 alleles;(4)This group of Rett syndrome combined with epilepsy can be controlled by levetiracetam and sodium valproate;(5)By analyzing the clinical phenotypes and genetics of the four cases of MECP2 gene mutation,the spectrum of the clinical phenotypes of MECP2 gene mutation was enriched.The link between the genotypes and phenotypes of the MECP2 gene mutation was strengthened.

关 键 词：MECP2基因 RETT综合征 癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]