Tu Emily, Bagnall Richard D, Duflou Johan, Semsarian Christopher
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute. Sydney Medical School, University of Sydney, Australia.
Brain Pathol. 2011 Mar;21(2):201-8. doi: 10.1111/j.1750-3639.2010.00438.x. Epub 2010 Sep 28.
Sudden unexpected death in epilepsy (SUDEP) is the most frequent epilepsy-related cause of death and is characterized by an absence of any identifiable cause of death at post-mortem, suggesting an underlying arrhythmogenic predisposition. This study sought to identify SUDEP cases in a review of post-mortem records and to undertake genetic studies in key familial long QT syndrome (LQTS) genes. All autopsies performed from 1993-2009 at a forensic centre in Sydney, Australia were reviewed and SUDEP cases identified. DNA was extracted from post-mortem blood and the three most common LQTS genes, ie, KCNQ1, KCNH2 (HERG) and SCN5A, were amplified and analyzed. Sixty-eight SUDEP cases were identified (mean age of 40 ± 16 years). Genetic analysis revealed 6 (13%) non-synonymous (amino acid changing) variants in KCNH2 (n = 2) and SCN5A (n = 4), all previously reported in LQTS patients. Specifically, KCNH2 Arg176Trp and SCN5A Pro1090Leu were identified once in SUDEP cases and absent in control alleles. Both DNA variants have been previously identified in the pathogenesis of LQTS. The cause of SUDEP is currently unknown. Our results indicate that investigation of key ion channel genes should be pursued in the investigation of the relationship between epilepsy and sudden death.
癫痫猝死（SUDEP）是癫痫相关死亡中最常见的原因，其特征是尸检时没有任何可识别的死因，提示存在潜在的致心律失常易感性。本研究旨在通过回顾尸检记录来识别SUDEP病例，并对关键的家族性长QT综合征（LQTS）基因进行遗传学研究。对1993年至2009年在澳大利亚悉尼一个法医中心进行的所有尸检进行了回顾，并确定了SUDEP病例。从尸检血液中提取DNA，对三个最常见的LQTS基因，即KCNQ1、KCNH2（HERG）和SCN5A进行扩增和分析。确定了68例SUDEP病例（平均年龄40±16岁）。遗传分析在KCNH2（n = 2）和SCN5A（n = 4）中发现了6个（13%）非同义（氨基酸改变）变异，这些变异均在LQTS患者中被报道过。具体而言，KCNH2 Arg176Trp和SCN5A Pro1090Leu在SUDEP病例中各被发现一次，在对照等位基因中未出现。这两种DNA变异此前均在LQTS的发病机制中被发现。SUDEP的病因目前尚不清楚。我们的结果表明，在研究癫痫与猝死之间的关系时，应进行关键离子通道基因的研究。
