Brugada综合征相关基因SCN5A新突变位点的检测

目的 研究中国人Brugada综合征相关基因SCN5A突变情况。方法 利用多聚酶链反应及DNA测序对1个Brugada综合征家系SCN5A基因的全部28个外显子进行基因检测。结果 在国内外已知突变点均无突变，发现1个新的错义突变位点(A5471G)，其相应的氨基酸改变为N1774S。结论 在中国人Brugada综合征患者的SCN5A基因上发现1个新的突变位点。     

Brugada综合征患者SCN5A基因突变检测

目的对体检中发现的两例无症状的Brugada综合征患者进行SCN5A基因突变检测。方法收集两个家系所有成员的外周血样标本,提取基因组DNA后应用聚合酶链式反应（PCR）扩增心脏电压门控钠通道蛋白α亚单位基因SCN5A的所有编码区序列,并直接进行DNA序列测定,若有碱基变异,则与200个正常样本进行对照,并分析相应的氨基酸改变。结果在一个患者的一条染色单体上发现SCN5A基因碱基变异:即第1712位密码子的第1个碱基的G→T改变,导致相应编码的甘氨酸（G）被半胱氨酸（C）所取代,而这一基因变异在200个正常人的对照中均未发现。家系调查发现患者的一个妹妹也具有相同的基因变异,但心电图无明显异常。结论在一个体检发现的Brugada综合征患者的SCN5A基因上发现一个未报道过的碱基变异,该碱基变异可能是新的基因突变位点。     

Brugada综合征一家系中2例患者的SCN5A基因突变及意义

目的 观察Brugada综合征一家系中2例患者的SCN5A基因突变情况,并探讨其意义.方法 选择Brugada综合征一家系2例患者,采用直接测序法对其SCN5A基因突变进行检测.结果 该家系中发现1个纯合变异,即SCN5A基因第28外显子上的同义变异（C5457T）,其所编码的1819位天冬氨酸密码子没有发生改变.结论 该Brugada综合征家系2例患者的SCN5A基因上存在1个同义变异,但SCN5A基因不是患者的致病基因.     

中国汉族人Brugada综合征患者SCN5A基因Ⅳ区一个新的突变

背景Brugada综合征是一种易导致猝死的具有遗传倾向的疾病，与编码心肌钠通道的基因突变有关。目的研究中国Brugada综合征患者SCN5A基因的碱基改变情况。方法对15例先证者及家系进行直接SCN5A基因测序。DNA来源于患者外周血白细胞。全部28个外显子通过设计的40对引物进行PCR扩增，扩增后的产物直接测序。结果在一个家系上发现了一个错义突变，即G5080A（R1628Q），该突变导致心肌细胞钠通道的α亚基第IV结构域的第4片段发生改变。在150个正常对照者未发现此碱基改变。结论G5080A（R1628Q）可能是中国Brugada综合征患者SCN5A基因新的突变位点。     

Brugada综合征SCN5A基因的三个新突变

目的 研究Brugada综合征相关基因SCN5A突变情况。方法 以4例Brugada综合征患者和9例临床可疑Brugada综合征患者为研究对象,采用聚合酶链反应和双脱氧末端终止测序法对所有患者进行SCNSA基因扫描。对阳性结果者进行家系中其他成员的筛查。结果 在1个Brugada综合征家系发现两个杂合突变,即SCN5A基因第3外显子上发现一错义突变（G283A）,导致代表缬氨酸残基的第95位密码子突变为异亮氨酸残基（V95I）,第28外显子上也发现一错义突变（CA946T）,导致代表丙氨酸的第1649位密码子突变为缬氨酸（A1649V）。在1个临床可疑Brugada综合征家系发现一杂合突变,即SCN5A基因第28外显子缺失3个碱基（TCT）,导致代表苯丙氨酸残基的第1617位密码子缺失（delF1617）。结论 在Brugada综合征患者发现了3个SCN5A基因新突变（V95I、A1649V、delF1617）。     

中国汉族人Brugada综合征患者SCN5A基因Ⅳ区一个新的突变

背景 Brugada 综合征是一种易导致猝死的具有遗传倾向的疾病,与编码心肌钠通道的基因突变有关。目的研究中国 Brulgada 综合征患者 SCN5A 基因的碱基改变情况。方法对15例先证者及家系进行直接SCN5A 基因测序。DNA 来源于患者外周血白细胞。全部28个外显子通过设计的40对引物进行 PCR 扩增,扩增后的产物直接测序。结果在一个家系上发现了一个错义突变,即 G5080A(R1628Q),该突变导致心肌细胞钠通道的α亚基第Ⅳ结构域的第4片段发生改变。在150个正常对照者未发现此碱基改变。结论 G5080A(R1628Q)可能是中国 Brugada 综合征患者 SCN5A 基因新的突变位点。     

中国散发Brugada综合征患者SCN5A基因突变位点的检测

目的 对5例中国散发Brugada综合征患者进行SCN5A基因突变位点检测.方法 采用直接测序法对5例散发Brugada综合征患者进行SCN5A基因碱基突变位点的检测,测序结果用Chromas软件进行BLAST分析,再将测序峰与网上检索结果重新比对.结果 1例Brugada患者发现了一个同义杂合变异,即SCN5A基因第20外显子上发现一个碱基变异（C3549T）,其所编码的第1 183位苏氨酸没有发生改变（T1183T）.结论 在中国散发Brugada综合征患者的SCN5A基因上发现了1个新的碱基杂合同义突变.     

发热诱导的Brugada波与SCN5A基因变异的研究

目的:探讨1例发热诱导的心电图Brugada波患者的临床特征并分析其与热敏感相关的SCN5A基因位点的变异情况。方法:分析1例50岁汉族男性发热诱导的Brugada波患者的临床表现,并采用PCR-直接测序法对与热敏感相关的SCN5A基因位点进行变异检测。结果:心电图示Brugada波改变,其抬高的ST段随体温控制逐渐回复。在基因变异研究中,未发现该患者的SCN5A基因存在与发热诱导的Brugada综合征有关的L325R(T→974G)、R535X(C→1603T)、H681P(A→2042C)和F1344S(T→4031C)4个突变。结论:该患者Brugada波的热敏感现象并非由SCN5A基因的4个变异位点引起,发热与Brugada波的关系复杂,有待深入研究。     

中国一家系Brugada综合征相关基因SCN5A突变位点的检测

目的研究一个中国家系Brugada综合征相关基因SCNSA的突变情况。方法收集一个Brugada家系的临床资料,采用聚合酶链反应及直接测序法对该家系进行SCN5A基因突变检测,同时对136例家系外健康对照者的该位点进行单链构象多态性分析。结果在Brugada家系中发现了两个杂合变异,即SCN5A基因第二外显子上发现一个同义变异（A129G）,没有导致氨基酸的改变（A29A）;第26外显子发现一个错义变异（T4492A）,导致代表酪氨酸的1494位密码子突变为天门冬酰胺（Y1494N）。结论在中国人Brugada综合征患者的SCNSA基因上发现了一个已经报道的同义多态位点（A29A）及一个新的错义突变位点（Y1494N）。     

中国汉族人Brugada综合征患者SON5A基因Ⅳ区一个新的突变

背景 Brugada综合征是一种易导致猝死的具有遗传倾向的疾病,与编码心肌钠通道的基因突变有关.目的 研究中国Brugada综合征患者SCN5A基因的碱基改变情况.方法 对15例先证者及家系进行直接SCN5A基因测序.DNA来源于患者外周血白细胞.全部28个外显子通过设计的40对引物进行PCR扩增,扩增后的产物直接测序.结果 在一个家系上发现了一个错义突变,即G5080A(R1628Q),该突变导致心肌细胞钠通道的α亚基第Ⅳ结构域的第4片段发生改变.在150个正常对照者未发现此碱基改变.结论 G5080A(R1628Q)可能是中国Brugada综合征患者SCN5A基因新的突变位点.     

Brugada syndrome with a novel missense mutation in SCN5A gene: A case report from Bangladesh

Brugada syndrome is an inherited cardiac arrhythmia that follows autosomal dominant transmission and can cause sudden death. We report a case of Brugada syndrome in a 55-year-old male patient presented with recurrent palpitation, atypical chest pain and presyncope. ECG changes were consistent with type 1 Brugada. Gene analysis revealed a novel missense mutation in SCN5A gene with a genetic variation of D785N and a nucleotide change at 2353G-A. One of his children also had the same mutation. To our knowledge this is the first genetically proved case of Brugada syndrome in Bangladesh.     

A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha subunit, which can lead ventricular fibrillation and sudden death. Inattentive use of antiarrhythmic drugs potentially triggers fatal cardiac arrhythmias through further reduction of sodium current (I(Na)). We studied the molecular mechanism underlying a case of Brugada syndrome that showed no response to a class Ic antiarrhythmic drug. Molecular genetic studies of a patient with Brugada syndrome identified a novel mutation in SCN5A, which causes substitution of serine for asparagine (N406S) in S6 of domain I (IS6). The provocation test with pilsicainide, a class Ic antiarrhythmic drug, failed to exacerbate ST-segment elevation in this case. Electrophysiological analyses of the N406S-mutant channel expressed together with the beta1 subunit in HEK293 cells showed that the voltage dependence of activation was positively shifted by 16 mV and that intermediate inactivation was enhanced. Whereas tonic block by pilsicainide was not changed in the N406S channel, use-dependent block by pilsicainide was almost completely abolished, consistent with the clinical findings of the negative provocation test. In contrast, the N406S channel showed stronger use-dependent block by quinidine than the wild-type channel. We demonstrate a novel Brugada mutation N406S, which is associated with the discordant effects on blocking actions of antiarrhythmic drugs as well as the multiple channel gating defects. We emphasis that an antiarrhythmic drug may exert unpredicted effects in patients with channel mutations.     

SCN5A基因突变与青壮年猝死综合征

青壮年猝死综合征(SUNDS)的病因迄今不明。随着分子遗传学和心脏离子通道研究的深入,SCN5A基因突变已被确定为Brugada综合征、3型长QT间期综合征的最重要病因。本文综述文献,结合项目组研究,介绍SCN5A基因突变与SUNDS发生的相关性。     

Homozygous SCN5A mutation in Brugada syndrome with monomorphic ventricular tachycardia and structural heart abnormalities.

AIMS: To describe a patient showing monomorphic ventricular tachycardia, ECG aspect of Brugada syndrome, and structural heart abnormalities due to a homozygous missense mutation in SCN5A. METHODS AND RESULTS: Thirteen subjects (six males, seven females, mean age 46 +/- 22 years) belonging to the same family underwent physical examination, basal biochemical marker detection, 12-lead ECG, Holter ECG, signal-averaged ECG, echocardiogram and genetic analysis. The proband underwent a stress test together with left and right ventricular angiography and electrophysiological study. Three subjects (the proband, his mother, and one brother) showed on ECG an ST-segment elevation in the right precordial leads with coved type aspect. Moreover, the proband presented a sustained monomorphic ventricular tachycardia (left bundle branch block aspect with superior axis), whereas all other family members were asymptomatic. Imaging techniques documented right ventricular structural abnormalities only in the proband. Mutation screening in SCN5A gene was performed in the proband and in available family members. The proband carries a novel SCN5A mutation, R814Q, in homozygous, whereas the parents and four siblings were heterozygous carriers of the same mutation. CONCLUSION: This study provides the first evidence of a homozygous missense mutation in SCN5A associated with atypical ventricular arrhythmias and right structural abnormalities.     

Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit, and potentially leads to ventricular fibrillation and sudden death. We report a case of a novel SCN5A mutation associated with Brugada syndrome. A 51-year-old man suffered from recurrent nocturnal syncopal attacks due to polymorphic ventricular tachycardia. His electrocardiogram showed ST-segment elevation in V1-V3 leads, but there was no evidence of structural heart disease. DNA sequence analysis of SCN5A in this patient revealed a missense mutation (R282H) in the S5-pore region of domain I. This mutational change was not present in 100 healthy Japanese controls. In the patient's family, a 36-year-old brother had died suddenly. Genetic analysis identified two other carriers of the R282H mutation, who had ST-segment elevation and slightly increased QRS widths, but they experienced no syncopal episodes or ventricular fibrillation. Electrophysiological investigation of the R282H mutant channel expressed in cultured cells showed a severe reduction in sodium current density and a mild positive shift of activation curve. R282H did not enhance intermediate inactivation. Single-channel conductance of R282H was slightly decreased compared with WT. The electrophysiological characteristics of the R282H channel are suggested to be closely related to the clinical phenotype of Brugada syndrome.