Long QT and Brugada syndrome gene mutations in New Zealand

被引:34
作者
Chung, Seo-Kyung
MacCormick, Judith M.
McCulley, Caroline H.
Crawford, Jackie
Eddy, Carey-Anne
Mitchell, Edwin A.
Shelling, Andrew N.
French, John K.
Skinner, Jonathan R.
Rees, Mark I.
机构
[1] Auckland Hosp, Paediat & Congen Cardiac Serv, Auckland 1030, New Zealand
[2] Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland, New Zealand
[3] Auckland Hosp, Cardiac Inherited Dis Grp, Auckland, New Zealand
[4] Starship Hosp, Greenlane Paediat & Congen Serv, Auckland, New Zealand
[5] Univ Auckland, Fac Med & Hlth Sci, Dept Obstet & Gynaecol, Auckland 1, New Zealand
[6] Univ Auckland, Dept Paediat, Auckland 1, New Zealand
[7] Liverpool Hosp, UNSW, Dept Cardiol, Sydney, NSW, Australia
[8] Swansea Univ, Sch Med, Inst Life Sci, Swansea, W Glam, Wales
关键词
long QT; mutations; arrhythmia; ion channels; sudden cardiac death;
D O I
10.1016/j.hrthm.2007.06.022
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1306 / 1314
页数:9
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