Kiehne Nadine, Kauferstein Silke
Zentrum der Rechtsmedizin, University of Frankfurt, Kennedyallee 104, D-60596 Frankfurt am Main, Germany.
Forensic Sci Int Genet. 2007 Jun;1(2):170-4. doi: 10.1016/j.fsigen.2007.01.009. Epub 2007 Feb 26.
Mutations in cardiac ion channel genes leading to channel dysfunctions or changes in the gene expression may cause inherited arrhythmogenic diseases. These genetic diseases are important causes of sudden unexplained death (SUD). Ten cases of SUD, including six cases of sudden infant death syndrome (SIDS) and four cases of SUD from people in the age of 14-40 years were examined by postmortem molecular analysis. Genomic DNA was extracted from blood cells and two long QT syndrome relevant genes, SCN5A encoding the alpha-subunit of the voltage-gated sodium channel Nav1.5 and KCNH2 encoding the alpha-subunit of the voltage-gated potassium channel HERG were selected for mutation analysis by complete gene sequencing. Various silent mutations in the KCNH2 and SCN5A genes as well as the known H558R polymorphism in SCN5A were detected. Moreover, sequence variations in the 3' untranslated region (3'UTR) and 5' untranslated region (5'UTR) of the SCN5A gene were observed. This study suggests that these areas are important regions to investigate the impact of changes in cardiac ion channel function on the risk of sudden unexpected death.
心脏离子通道基因突变导致通道功能障碍或基因表达改变，可能会引发遗传性心律失常疾病。这些遗传性疾病是不明原因猝死（SUD）的重要原因。通过尸检分子分析对10例SUD病例进行了检查，其中包括6例婴儿猝死综合征（SIDS）和4例14至40岁人群的SUD病例。从血细胞中提取基因组DNA，并选择两个与长QT综合征相关的基因进行突变分析，这两个基因分别是编码电压门控钠通道Nav1.5α亚基的SCN5A和编码电压门控钾通道HERGα亚基的KCNH2，采用全基因测序法进行分析。在KCNH2和SCN5A基因中检测到各种沉默突变以及SCN5A基因中已知的H558R多态性。此外，还观察到SCN5A基因3'非翻译区（3'UTR）和5'非翻译区（5'UTR）的序列变异。本研究表明，这些区域是研究心脏离子通道功能变化对意外猝死风险影响的重要区域。
