厦门地区三例Brugada综合征患者SCN5A基因突变分析  

Analysis of SCN5A Gene Mutation in Three Patients with Brugada Syndrome in Xiamen

作　　者：葛高顺 林玲[2] 倪二茹 谢华斌 GE Gao-shun;LIN Ling;NI Er-ru;XIE Hua-bin(Department of Laboratory Medicine,Cardiovascular Hospitals of Xiamen University/Xiamen Key Laboratory of Precision Medicine for Cardiovascular Disease,Fujian Xiamen 361009,China;Department of Laboratory Medicine,Xiamen Hospital of Tradional Chinese Medicine,Fujian Xiamen 361010,China)

机构地区：[1]厦门大学附属心血管病医院检验科/厦门市心血管疾病精准医学重点实验室,福建厦门361009 [2]厦门市中医院检验科,福建厦门361010

出　　处：《现代检验医学杂志》2023年第2期81-85,101,共6页Journal of Modern Laboratory Medicine

摘　　要：目的探讨厦门地区3例Brugada综合征患者SCN5A基因突变情况。方法选取2011年1月~2022年6月到厦门大学附属心血管病医院就诊的3例Brugada综合征患者作为观察组,同期20例健康体检者作为对照组,收集两组人群的常规生化与心肌标志物检测结果。采集观察组全血后提取基因组DNA,应用高通量测序平台对Brugada综合征相关基因的目标区域测序,再预测蛋白质三维结构,比较国内已报道的Brugada综合征相关新发疑似致病SCN5A基因突变。结果观察组与对照组的常规生化与心肌标志物检测结果均无明显差异,目标区域捕获测序结果显示有2位受检者都携带SCN5A c·219delA移码突变,该突变导致74位的谷氨酸变成了丝氨酸,并产生新的阅读框架,终止于第74号密码子下游23位密码子处,产生一个缩短并变异的RNA以及蛋白。另一位受检者携带SCN5A c·584G>A无义突变,该突变会导致编码蛋白序列提前终止,产生一个截短的蛋白,可能会对蛋白质的结构和功能产生较大影响。这两个点突变都未有文献报道,在各大公共数据库中均没有被检索到,根据美国医学遗传学与基因组学协会(ACMG)评估指南,定义该位点为疑似致病突变的变异。结论SCN5A c·219delA和SCN5A c·584G>A点突变是Brugada综合征的致病原因。Objective To explore the SCN5A gene mutations in 3 patients with Brugada syndrome in Xiamen.Methods From January 2011 to June 2022,3 patients with Brugada syndrome who went to the Cardiovascular Hospital of Xiamen University were selected as the observation group,and 20 patients with healthy physical examination during the same period were selected as the control group,and the routine biochemical and myocardial marker detection results of the two group were collected.The whole blood of the observation group was collected to extracte the genomic DNA,and the target regions of Brugada syndromerelated genes was sequenced using the high-throughput sequencing platform,then the three-dimensional structure of the protein was predicted,and the mutations of the newly suspected pathogenic SCN5A gene related to Brugada syndrome-reported in China were compared.Results There were no significant differences in the results of biochemical and myocardial markers between the two groups.Target region capture sequencing showed that two observation patients carried SCN5A c·219delA frameshift mutation,changed the glutamate at position 74 to serine and produced a new reading frame,which terminated at codon 74 downstream codon 23,resulting in a shortened and mutated RNA and protein.The other observation patient carried SCN5A c·584G>A anonsense mutation,which caused premature termination of the coding protein sequence,produced a truncated protein,which could had a significant impact on the structure and function of the protein.These two mutations had not been reported in the previous literature and databases.According to the American College of Medical Genetics and Genomics(ACMG)assessment guidelines,these two mutations were defined as suspected pathogenic mutations.Conclusion SCN5A c·219delA and SCN5A c·584G>A were found in this study may be the causative cause of Brugada syndrome.

关 键 词：BRUGADA综合征 SCN5A 厦门 

分 类 号：R541.78[医药卫生—心血管疾病] Q754[医药卫生—内科学]