title: Genetic screening in sudden cardiac death in the young can save future lives.
abstract: BACKGROUND
  Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds.
  
  
  RESULTS
  From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40%). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT).
  
  
  CONCLUSIONS
  Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.
authors.affiliation: Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden. eva-lena.stattin@umu.se.
authors.forename: Eva-Lena
authors.identifier: http://orcid.org/0000-0002-9661-2591
authors.initials: EL
authors.lastname: Stattin
authors.affiliation: Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
authors.forename: Ida Maria
authors.initials: IM
authors.lastname: Westin
authors.affiliation: Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Cederquist
authors.affiliation: Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
authors.forename: Jenni
authors.initials: J
authors.lastname: Jonasson
authors.affiliation: Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
authors.forename: Björn-Anders
authors.initials: BA
authors.lastname: Jonsson
authors.affiliation: Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Stellan
authors.initials: S
authors.lastname: Mörner
authors.affiliation: Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Norberg
authors.affiliation: Department of Forensic Medicine, Lund University, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Krantz
authors.affiliation: Department of Internal Medicine, Sunderby Hospital, Luleå, Sweden.
authors.forename: Aase
authors.initials: A
authors.lastname: Wisten
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D053803:Forensic Genetics; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D009154:Mutation; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D017180:Tachycardia, Ventricular / Q000235:genetics*; D055815:Young Adult; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: Catecholaminergic polymorphic ventricular tachycardia; Long QT syndrome; Molecular autopsy; Sudden cardiac death; Sudden unexplained death