title: 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.
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 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.
authors.affiliation: Department of Legal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan. leg010@art.osaka-med.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Nishio
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsubone
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Koda
authors.forename: Takako
authors.initials: T
authors.lastname: Sato
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukunishi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Tamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: 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
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human