结节性硬化症TSC1和TSC2基因型与临床表型相关性研究  

Correlation of TSC1 and TSC2 genotype with clinical phenotype in tuberous sclerosis

作　　者：梅道启 符娜 秦炯[2] MEI Daoqi;FU Na;QIN Jiong(Eastern Neurology Department,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou 450018,Henan,China;Pediatric Department,Peking University People’s Hospital,Beijing 100044,China)

机构地区：[1]郑州大学附属儿童医院河南省儿童医院郑州儿童医院东区神经内科,河南郑州450018 [2]北京大学人民医院儿科,北京100044

出　　处：《临床儿科杂志》2018年第9期678-682,共5页Journal of Clinical Pediatrics

基　　金：科技部支撑计划课题(No.2012BAI03B02);国家科技部重大研究专项(No.2016YFC0904400)

摘　　要：目的探讨结节性硬化症TSC1和TSC2基因型与临床表型相关性。方法对2016年8月至2017年8月就诊的30例临床诊断为结节性硬化症的患儿行TSC1、TSC2基因分析,并进行基因型-表型关系分析。结果 30例患儿中,男22例、女8例,中位年龄6.45岁。5例发现TSC1基因突变、22例发现TSC2基因突变,突变率90%。TSC1和TSC2基因突变类型有5种,错义突变、无义突变、大片段缺失、移码突变和剪切突变,以无义突变、剪切突变和移码突变的发生率最高。其中TSC1基因仅发现剪切突变和移码突变;TSC2基因上述5种突变均有发现。共发现12种结节性硬化症的临床表型,其中以面部血管纤维瘤、癫痫和智力低下的发生率最高。癫痫发生在TSC2和TSC1基因型之间的差异有统计学意义(P<0.05)。结论结节性硬化症临床表型和突变类型较多,TSC2基因突变频率大于TSC1基因,TSC2基因突变更易引发严重的结节性硬化症的临床表现。Objective To explore the correlation of TSC1 and TSC2 genotype with clinical phenotype in tuberous sclerosis.Method The TSC1 and TSC2 gene analysis were performed in 30 children from August 2016 to August 2017,and the relationship between genotype and phenotype was analyzed.Results In 30 children with tuberous sclerosis(22 males and 8 females)with a median age at 6.45 years,TSC1 gene mutation was found in 5 cases,and TSC2 gene mutation in 22 cases.A mutation rate was 90%.There were 5 types of mutations in TSC1 and TSC2 genes including missense mutation,nonsense mutation,large fragment deletion,frameshift mutation and shear mutation,and the incidence rates of nonsense mutations,shear mutations and transcoding mutations were the highest.Only shear mutation and frameshift mutation were found in TSC1 gene.All the above 5 mutations were found in TSC2 gene.A total of 12 clinical phenotypes of tuberous sclerosis were found and the facial angiofibroma,epilepsy and mental retardation had highest incidence.There was statistical difference in the incidence of epilepsy between the TSC2 and TSC1 genotypes(P<0.05).Conclusions There are many clinical phenotypes and mutation types in tuberous sclerosis.The mutation frequency of TSC2 gene is higher than that of TSC1 gene,and the mutation of TSC2 gene is more likely to cause severe clinical manifestations of tuberous sclerosis.

关 键 词：结节性硬化症 TSC1基因 TSC2基因 临床表型 

分 类 号：R725.9[医药卫生—儿科]