Identification of an ethnic-specific variant (V207M) of the KCNQ1 cardiac potassium channel gene in sudden unexplained death and implications from a knock-in mouse model
Identification of an ethnic-specific variant (V207M) of the KCNQ1 cardiac potassium channel gene in sudden unexplained death and implications from a knock-in mouse model
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DOI：
10.1007/s00414-009-0321-3
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发表时间：
2009-05-01
影响因子：
2.1
通讯作者：
Suzuki, Koichi
中科院分区：
文献类型：
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作者：
Nishio, Hajime;Kuwahara, Masayoshi;Suzuki, Koichi
我们对17例不明原因猝死尸检病例中涉及长QT综合征的基因（KCNQ 1、KCNH 2和SCN 5A）进行了突变分析。单链构象多态性和随后的DNA测序分析显示，在一个案例中，有一个变异，V207 M的KCNQ 1，编码心脏钾通道的基因。该病例为一名40岁非洲男性，被证明具有杂合错义突变（V207 M），该突变先前已报告为种族特异性。在444个等位基因中，有1例（0.23%）非洲人V207 M杂合子突变。我们开发了一种Kcnq 1-V206 M突变的敲入小鼠模型载体，该小鼠相当于在受害者中鉴定的KCNQ 1-V207 M突变。在Kcnq 1（V206 M/V206 M）小鼠中观察到QT间期显著延长。这些发现表明，KCNQ 1-V207 M突变可能是致病性的，并可能与本案的死亡原因有关。
We performed mutation analysis for genes implicated in long QT syndrome (KCNQ1, KCNH2, and SCN5A) in 17 sudden unexplained death autopsy cases. Single-strand conformation polymorphism and subsequent DNA sequencing analyses revealed that in one case, there was a variant, V207M of KCNQ1, a gene encoding a cardiac potassium channel. This case, a 40-year-old African male, was shown to have a heterozygous missense mutation (V207M), which has been previously reported to be ethnic-specific. The heterozygous V207M mutation was found in one case (0.23%) of 444 alleles from African individuals. We developed a knock-in mouse model carrier of the Kcnq1-V206M mutation, the mouse equivalent to the KCNQ1-V207M mutation identified in the victim. Significant prolongation of QT intervals was observed in the Kcnq1(V206M/V206M) mice. These findings suggest that the KCNQ1-V207M mutation might be pathogenic and might have been associated with the cause of death in the present case.