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.
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.
Nishio
Hajime
H
Department of Legal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan. leg010@art.osaka-med.ac.jp
Kuwahara
Masayoshi
M
Tsubone
Hirokazu
H
Koda
Yoshiro
Y
Sato
Takako
T
Fukunishi
Shinya
S
Tamura
Akiyoshi
A
Suzuki
Koichi
K
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D004562:Electrocardiography; D005091:Exons / Q000235:genetics; D005260:Female; D055879:Gene Knock-In Techniques; D006580:Genetic Carrier Screening; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population; D006720:Homozygote; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D020125:Mutation, Missense; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human