title: The role of known variants of KCNQ1, KCNH2, KCNE1, SCN5A, and NOS1AP in water-related deaths.
abstract: Drowning is one of the most frequent causes of accidental deaths worldwide, and still it remains a diagnosis of exclusion. Moreover, sudden cardiac deaths (SCD) or, if no actual cardiac alterations can be found, sudden unexplained deaths (SUD) represent a major group within mortality statistics as well. This leads to the assumption that there might be a general underlying cause for at least some cases of drowning, SCD, or SUD, for example, genetic aberrations in arrhythmia-associated genes. In the present study, blood samples of 171 corpses found in water (drowning, death after almost drowning, and unclear deaths) were analyzed in 19 known variants of the genes KCNQ1, KCNH2, KCNE1, SCN5A, and NOS1AP by minisequencing. In three variants of NOS1AP, significant differences of allele and/or genotype frequencies could be demonstrated between victims of drowning and published controls as well as own controls. Moreover, similar differences were found comparing unexplained deaths in water and controls. Regarding the other genes, especially one single nucleotide polymorphism (SNP) of KCNQ1 could be associated with drowning. These results propose that performing a molecular autopsy analyzing known variants of arrhythmia-associated genes, in particular NOS1AP, may assist in establishing a cause of death for bodies found in water without clear drowning signs.
authors.affiliation: Institute of Legal Medicine, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Iliana
authors.initials: I
authors.lastname: Tzimas
authors.affiliation: Institute of Legal Medicine, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Jana-Christin
authors.initials: JC
authors.lastname: Zingraf
authors.affiliation: Institute of Legal Medicine, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bajanowski
authors.affiliation: Institute of Legal Medicine, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. micaela.poetsch@uk-essen.de.
authors.forename: Micaela
authors.identifier: http://orcid.org/0000-0003-1364-6487
authors.initials: M
authors.lastname: Poetsch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D053447:Channelopathies / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004332:Drowning / Q000175:diagnosis*; D000072237:ERG1 Potassium Channel / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072237:ERG1 Potassium Channel; C489622:KCNE1 protein, human; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; C488081:NOS1AP protein, human; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human
keywords: Arrhythmia; Drowning; KCNQ1; Long QT syndrome; NOS1AP; Variants