Long QT and Brugada syndrome gene mutations in New Zealand
Long QT and Brugada syndrome gene mutations in New Zealand
复制标题
DOI：
10.1016/j.hrthm.2007.06.022
复制
发表时间：
2007-10-01
期刊：
影响因子：
5.5
通讯作者：
Rees, Mark I.
中科院分区：
文献类型：
--
作者：
Chung, Seo-Kyung;MacCormick, Judith M.;Rees, Mark I.
背景童QT综合征(LQTS)的基因检测正从研究走向临床实践。我们最近在新西兰的一个研究实验室进行了分子遗传学试验，以期建立临床诊断服务。目的本研究旨在报告新西兰LQTS基因试验计划确定的LQTS和Brugada突变的谱。方法对来自新西兰和澳大利亚的84例连续进行LQT基因测试的索引病例进行评估。结果43例患者共检出45个LQTS突变，其中KCNQ1突变25个(9个新突变)，Herg突变13个(7个新突变)，SCN5A突变7个(7个新突变)。LQTS 40例，Brugada综合征3例。在14例复苏性心脏性猝死患者中发现突变：4例KCNQ1，5例HERG，5例SCN5A。17例有一级亲属心脏性猝死家族史：8例KCNQ1，6例HERG，2例SCN5A，1例同时存在KCNQ1和HERG突变。结论新西兰LQTS和Brugada基因突变谱与已有研究相似。新突变的高比例(40%)表明需要确认局部流行突变的致病性。仔细的筛查选择标准、对新突变的细胞功能分析以及发展当地相关的对照样本队列，都将是建立区域诊断服务的关键。
BACKGROUND Genetic testing in tong QT syndrome (LQTS) is moving from research into clinical practice. We have recently piloted a molecular genetics program in a New Zealand research laboratory with a view to establishing a clinical diagnostic service.OBJECTIVE This study sought to report the spectrum of LQTS and Brugada mutations identified by a pilot LQTS gene testing program in New Zealand.METHODS Eighty-four consecutive index cases referred for LQT gene testing, from New Zealand and Australia, were evaluated. The coding sequence and splice sites of 5 LQTS genes (KCNQ1, HERG, SCN5A, KCNE1, and KCNE2) were screened for genomic variants by transgenomics denaturing high-performance liquid chromatography (dHPLC) system and automated DNA sequencing.RESULTS Forty-five LQTS mutations were identified in 43 patients (52% of the cohort): 25 KCNQ1 mutations (9 novel), 13 HERG mutations (7 novel), and 7 SCN5A mutations (2 novel). Forty patients had LQTS, and 3 had Brugada syndrome. Mutations were identified in 14 patients with resuscitated sudden cardiac death: 4 KCNQ1, 5 HERG, 5 SCN5A. In 17 cases there was a family history of sudden cardiac death in a first-degree relative: 8 KCNQ1, 6 HERG, 2 SCN5A, and 1 case with mutations in both KCNQ1 and HERG.CONCLUSION The spectrum of New Zealand LQTS and Brugada mutations is similar to previous studies. The high proportion of novel mutations (40%) dictates a need to confirm pathogenicity for locally prevalent mutations. Careful screening selection criteria, cellular functional analysis of novel mutations, and development of locally relevant control sample cohorts will all be essential to establishing regional diagnostic services.