title: Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy.
abstract: The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart.
authors.affiliation: Department of Forensic Medicine, Faculty of Health Sciences, Aarhus University, Aarhus N, Denmark. ml@forensic.au.dk
authors.forename: M K
authors.initials: MK
authors.lastname: Larsen
authors.forename: P H
authors.initials: PH
authors.lastname: Nissen
authors.forename: K E
authors.initials: KE
authors.lastname: Berge
authors.forename: T P
authors.initials: TP
authors.lastname: Leren
authors.forename: I B
authors.initials: IB
authors.lastname: Kristensen
authors.forename: H K
authors.initials: HK
authors.lastname: Jensen
authors.forename: J
authors.initials: J
authors.lastname: Banner
mesh_terms: D000293:Adolescent; D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D053803:Forensic Genetics; D005820:Genetic Testing; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D051191:Plakophilins / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D034904:Lamin Type A; D008565:Membrane Proteins; D018995:Myosin Heavy Chains; D051191:Plakophilins; D000099163:Myosin Binding Protein C; C494847:LMNA protein, human; C501641:MYH7 protein, human; C495337:PKP2 protein, human; C528696:TMEM43 protein, human