title: Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.
abstract: BACKGROUND
  Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases.
  
  
  RESULTS
  Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively.
  
  
  CONCLUSIONS
  Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Olallo
authors.initials: O
authors.lastname: Sanchez
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).|Department of Medical Sciences, School of Medicine, University of Girona, Girona (Spain).
authors.forename: Oscar
authors.identifier: http://orcid.org/0000-0001-5298-5276
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).|Cardiovascular Genetics Unit, Hospital Josep Trueta, Girona (Spain).
authors.forename: Anna
authors.initials: A
authors.lastname: Fernández-Falgueras
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona (Spain).
authors.forename: Georgia
authors.initials: G
authors.lastname: Sarquella-Brugada
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona (Spain).
authors.forename: Sergi
authors.initials: S
authors.lastname: Cesar
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Irene
authors.initials: I
authors.lastname: Mademont
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Jesus
authors.initials: J
authors.lastname: Mates
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pérez-Serra
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Monica
authors.initials: M
authors.lastname: Coll
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Ferran
authors.initials: F
authors.lastname: Pico
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Cardiovascular Genetics Unit, Hospital Josep Trueta, Girona (Spain).
authors.forename: Coloma
authors.initials: C
authors.lastname: Tirón
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona (Spain).
authors.forename: Esther
authors.initials: E
authors.lastname: Carro
authors.affiliation: Forensic Pathology Service, Institut Medicina Legal Ciències Mèdiques Catalunya, Barcelona (Spain).
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Gallego
authors.affiliation: Gendiag SL, Barcelona (Spain).
authors.forename: Carles
authors.initials: C
authors.lastname: Ferrer-Costa
authors.affiliation: Forensic Pathology Service, Institut Medicina Legal i Ciències Forenses de Catalunya, Girona (Spain).
authors.forename: Anna
authors.initials: A
authors.lastname: Hospital
authors.affiliation: Forensic Pathology Service, Institut Medicina Legal i Ciències Forenses de Catalunya, Girona (Spain).
authors.forename: Narcís
authors.initials: N
authors.lastname: Bardalet
authors.affiliation: Histopathology Unit, Instituto Nacional de Toxicología y Ciencias Forenses, Barcelona (Spain).
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Borondo
authors.affiliation: Histopathology Unit, Instituto Nacional de Toxicología y Ciencias Forenses, Barcelona (Spain).
authors.forename: Albert
authors.initials: A
authors.lastname: Vingut
authors.affiliation: Arrhythmia Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona (Spain).
authors.forename: Elena
authors.initials: E
authors.lastname: Arbelo
authors.affiliation: Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona (Spain).|Arrhythmia Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona (Spain).
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Forensic Pathology Service, Institut Medicina Legal Ciències Mèdiques Catalunya, Barcelona (Spain).
authors.forename: Josep
authors.initials: J
authors.lastname: Castellà
authors.affiliation: Forensic Pathology Service, Institut Medicina Legal Ciències Mèdiques Catalunya, Barcelona (Spain).
authors.forename: Jordi
authors.initials: J
authors.lastname: Medallo
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain).|Department of Medical Sciences, School of Medicine, University of Girona, Girona (Spain).|Cardiovascular Genetics Unit, Hospital Josep Trueta, Girona (Spain).
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003645:Death, Sudden; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D055815:Young Adult