title: Postmortem genetic testing should be recommended in sudden cardiac death cases due to thoracic aortic dissection.
abstract: BACKGROUND
  Acute thoracic aortic dissections and ruptures, the main life-threatening complications of the corresponding aneurysms, are an important cause of sudden cardiac death. Despite the usefulness of the molecular diagnosis of these conditions in the clinical setting, the corresponding forensic field remains largely unexplored. The main goal of this study was to explore and validate a new massive parallel sequencing candidate gene​ assay as a diagnostic tool for acute thoracic aortic dissection autopsy cases.
  
  
  METHODS
  Massive parallel sequencing of 22 thoracic aortic disease candidate genes performed in 17 cases of thoracic aortic dissection using AmpliSeq and Ion Proton technologies. Genetic variants were filtered by location, type, and frequency at the Exome Aggregation Consortium and an internal database and further classified based on the American College of Medical Genetics and Genomics (ACMG) recommendations published in 2015. All prioritized results were confirmed by traditional sequencing.
  
  
  RESULTS
  From the total of 10 potentially pathogenic genetic variants identified in 7 out of the 17 initial samples, 2 of them were further classified as pathogenic, 2 as likely pathogenic, 1 as possibly benign, and the remaining 5 as variants of uncertain significance, reaching a molecular autopsy yield of 23%, approximately.
  
  
  CONCLUSIONS
  This massive parallel sequencing candidate gene approach proved useful for the molecular autopsy of aortic dissection sudden cardiac death cases and should therefore be progressively incorporated into the forensic field, being especially beneficial for the anticipated diagnosis and risk stratification of any other family member at risk of developing the same condition.
authors.affiliation: Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Gago-Díaz
authors.affiliation: Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ramos-Luis
authors.affiliation: Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.|Laboratorio di Genetica Forense, Sezione di Medicina Legale, Dipartimento S.A.I.M.L.A.L., Università di Roma Sapienza, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zoppis
authors.affiliation: Servicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Zorio
authors.affiliation: Servicio de Patología, Instituto de Medicina Legal de Valencia, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Molina
authors.affiliation: Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Aitana
authors.initials: A
authors.lastname: Braza-Boïls
authors.affiliation: Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Juan
authors.initials: J
authors.lastname: Giner
authors.affiliation: Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sobrino
authors.affiliation: Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Amigo
authors.affiliation: Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Blanco-Verea
authors.affiliation: Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.|Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Carracedo
authors.affiliation: Xenética de Enfermidades Cardiovasculares e Oftalmolóxicas, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. maria.brion@usc.es.|Grupo de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela, Universidade de Santiago de Compostela, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain. maria.brion@usc.es.|Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Laboratorio 1, Travesía de Choupana S/N, CP: 15706, Santiago de Compostela, Spain. maria.brion@usc.es.
authors.forename: María
authors.initials: M
authors.lastname: Brion
mesh_terms: D000784:Aortic Dissection / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D053803:Forensic Genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000592:standards*; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans
keywords: Acute thoracic aortic disease; Candidate genes; Massive parallel sequencing; Molecular autopsy