癫痫杂志

癫痫杂志

547例Dravet综合征患儿SCN1A基因突变与遗传特点研究

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目的研究Dravet综合征(Dravet syndrome, DS)患儿SCN1A基因突变与遗传特点, 分析家系成员临床表型 方法收集2005年2月-2015年4月在北京大学第一医院儿科就诊的DS患儿及其家系成员的临床资料及外周血DNA, 采用Sanger测序和多重连接依赖的探针扩增技术(Multiple ligation-dependent probe amplification, MLPA)进行SCN1A基因突变筛查。 结果共收集547例DS患儿, 有379例(69.3%)发现SCN1A基因突变, 其中错义突变179例(47.2%), 无义突变78例(20.6%), 移码突变77例(20.3%), 剪切位点突变37例(9.8%), 基因片段缺失或重复8例(2.1%)。379例SCN1A突变阳性的DS患儿中, 354例均获得其父母外周血DNA, 证实新生突变占92.9%(329/354), 遗传性突变占7.1%(25/354), 遗传性突变包括5例父母一方为突变嵌合体。25例携带突变的父母一方中有1例表型为DS, 11例表型为热性惊厥附加症, 9例表型为热性惊厥, 4例表型正常。 结论DS患儿SCN1A基因突变阳性率高, 突变类型以错义突变和截断突变(包括无义突变和移码突变)为主, 少数患儿为该基因片段缺失或重复; DS患儿SCN1A基因突变以新生突变为主, 少数为遗传性突变, 父母一方可为该基因突变嵌合体; 携带突变的父母一方表型轻重不等, 父母一方为突变嵌合体者临床表型轻或正常。

ObjectiveTo study SCN1A gene mutations and their inheritance in patients with Dravet syndrome (DS), and to analyze the phenotypes of their family members. MethodsGenomic DNA was extracted from peripheral blood samples from DS patients and their parents. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Results547 DS patients were collected, SCN1A gene mutations were identified in 379 patients (69.3%), which included 179 missense mutations (47.2%), 78 nonsense mutations (20.6%), 77 frameshift mutations (20.3%), 37 splice site mutations (9.8%), and 8 cases with SCN1A gene fragment deletions or duplications (2.1%). Of 379 DS patients, the parents of 354 DS patients were further analyzed, the de novo mutations accounted for 92.9%, inherited mutations accounted for 7.1%, and in 5 of the latter families, the SCN1A-positive parent carried a somatic mutations mosaicism. For the 25 parents carrying SCN1A mutations, 1 had DS, 11 had febrile seizures plus, 9 had febrile seizures, whilst 4 were normal. ConclusionsThe mutation rate of SCN1A in DS patients is high. Most mutations are of missense and truncation mutations (including nonsense mutation and frameshift mutation). Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few are inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations can be severe, mild or normal, and a mosaic transmitting parent always shows mild or normal.

关键词: Dravet综合征; SCN1A基因; 新生突变; 遗传性突变; 突变嵌合体

Key words: Dravet syndrome; SCN1A gene; De novo mutation; Inherited mutation; Mosaic

引用本文: 田小娟, 张月华, 杨小玲, 许小菁, 刘爱杰, 刘晓燕, 杨志仙, 吴晔, 姜玉武, 吴希如. 547例Dravet综合征患儿SCN1A基因突变与遗传特点研究. 癫痫杂志, 2016, 2(1): 3-8. doi: 10.7507/2096-0247.20160001 复制

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