Abstract
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 Kcnq1V206M/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.
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Acknowledgments
We thank Dr. Yoshiro Sohma and Dr. Tomohiko Ai for their valuable comments. We also thank Ms. Misa Iwata for technical assistance in the mutation analysis. This work was supported by a grant-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan.
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Nishio, H., Kuwahara, M., Tsubone, H. et al. 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. Int J Legal Med 123, 253–257 (2009). https://doi.org/10.1007/s00414-009-0321-3
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DOI: https://doi.org/10.1007/s00414-009-0321-3