Dravet综合征SCN1A基因突变的遗传特点及表型研究  

Genetic and phenotypic characteristics of SCN1A mutations in Dravet syndrome

作　　者：许小菁[1] 张月华[1] 孙慧慧[2] 刘晓燕[1] 姜玉武[1] 吴希如[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]北京积水潭医院儿科

出　　处：《中华医学遗传学杂志》2012年第6期625-630,共6页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（81171221）

摘　　要：目的研究Dravet综合征（Dravetsyndrome，DS）患儿SCN1A基因突变类型和遗传特点，分析家系受累成员临床表型及基因型与表型相关性。方法收集181例DS患儿及其父母临床资料及外周血DNA，对父母是受累者的临床表型进行分析，并采用PCR—DNA直接测序和多重连接依赖的探针扩增技术进行SCN1A基因突变筛查。结果共发现128例患儿有SCN1A突变，突变率占70．7％（128／181）。其中包括60例（46．9％）错义突变，55例（43．0％）截断突变，10例（7．8％）剪切位点突变，3例（2．3％）有SCN1A基因片段缺失或重复。证实5例患儿其突变（Y349C、T1658M、T841fsx842、w190R、C373fsx378）遗传自父母一方，遗传突变占3．9％（5／128），其中1例父亲为突变嵌合体（C373fsx378）。5例携带突变的父母一方中，1例表型正常，其余4例表型包括热性惊厥1例，热性惊厥附加症2例，无热的全面强直阵挛发作1例。结论DS患儿SCN1A基因突变率较高，突变类型以错义突变、截断突变为主，少数患儿为SCN1A基因片段缺失或重复。DS患儿SCN1A基因突变以新生突变为主，少数为来源于父母一方的遗传性突变，父母可为sCNIA突变嵌合体，携带突变的父母一方表型正常或较轻。Objective To study SCNIA gene mutations and their inheritance in patients with Dravet syndrome （DS）, and to analyze the phenotypes of their family members and genotype-phenotype correlations. Methods Genomic DNA was extracted from peripheral blood samples from 181 DS patients and their parents. Phenotypes of affected members were analyzed. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification （MLPA）. Results SCNIA gene mutations were identified in 128 patients （70. 7%）, which included 60 missense mutations （46.9%）, 55 truncation mutations （43.0%）, 10 splice site mutations （7.8%）, and 3 cases with SCN1A gene fragment deletions or duplications （2.3 %）. Five patients （3.9% ） had mutations inherited from one of their parents. One father has carried a somatic mutation mosaicism （C373fsx378）. For the 5 parents carrying a mutation, 1 had febrile seizures, 2 had febrile seizures plus, 1 had afebrile generalized tonic-clonic seizures, whilst 1 was normal. Conclusion The mutation rate of SCN1A in DS patients is about 70%. Most mutations are of missense and truncation mutations. Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few were inherited from the parents. SCNIA mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCNIA mutations are either mild or normal.

关 键 词：DRAVET综合征 SCN1A基因 突变 嵌合体 

分 类 号：R742.1[医药卫生—神经病学与精神病学]