【摘要】 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SCN5A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(C4946T),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、ddF1617)。更多还原

【Abstract】 Objective Brugada syndrome is an inherited channelopathy that characterized by ST-segment elevation in the right precordial lead (V1-V3) on the electrocardiogram with or without right bundle branch block and related with high risk of sudden cardiac death and structurally normal hearts. The first and only gene linked to this disease is SCN5A, a gene encodes for a subunit of the cardiac sodium channel. The objective of this study is to explore SCN5A gene mutations in Chinese patients with Brugada syndrome. Methods Four patients diagnosed as Brugada syndrome and nine patients with suspected Brugada syndrome were chosen for the study. The exons in the functional regions of SCN5A gene were amplified with polymerase chain reaction and the amplified products were sequenced with Sanger method. If a mutation was identified, patient’s family members were also screened. Results Two heterozygous mutations were found in one family diagnosed as Brugada syndrome. One missense mutation was a G→A transition in the first nucleotide of codon 95 in SCN5A gene exon 3, which was predicted to result in substitution of Valine with Isoleucine (V95I). The other missense mutation was a C→T transition in the second nucleotide of codon 1649 in SCN5A gene exon 28, which was predicted to result in substitution of Alanine with Valine ( A1649V). A heterozygous mutation was identified in one family suspected to have the disease. The mutation was a three nucleotides (TCT) deletion that caused Phenylalanine deletion in codon 1617 in SCN5A gene exon 28. The three mutations were not detected in 100 control chromosomes. Conclusions Mutation in SCN5A gene is one of the causes of Brugada syndrome in Chinese. Three novel SCN5A gene mutations were identified in Chinese with Brugada syndrome, which expands the spectrum of SCN5A mutations associated with the disease.更多还原