title: Genotype-phenotype dilemma in a case of sudden cardiac death with the E1053K mutation and a deletion in the SCN5A gene.
abstract: Mutations in the cardiac sodium channel gene SCN5A may result in various arrhythmia syndromes such as long QT syndrome type 3 (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), cardiac conduction diseases (CCD) and possibly dilated cardiomyopathy (DCM). In most of these inherited cardiac arrhythmia syndromes the phenotypical expression may range from asymptomatic phenotypes to sudden cardiac death (SCD). A 16-year-old female died during sleep. Autopsy did not reveal any explanation for her death and a genetic analysis was performed. A variant in the SCN5A gene (E1053K) that was previously described as disease causing was detected. Family members are carriers of the same E1053K variant, some even in a homozygous state, but surprisingly did not exhibit any pathological cardiac phenotype. Due to the lack of genotype-phenotype correlation further genetic studies were performed. A novel deletion in the promoter region of SCN5A was identified in the sudden death victim but was absent in other family members. These findings demonstrate the difficulties in interpreting the results of a family-based genetic screening and underline the phenotypic variability of SCN5A mutations.
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Frankfurt am Main, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Jenewein
authors.affiliation: University Hospital Munich, Department of Medicine I, Ludwig Maximilians University, Munich, Germany; German Cardiovascular Research Center (DZHK), Partner Site: Munich Heart Alliance, Munich, Germany.
authors.forename: B M
authors.initials: BM
authors.lastname: Beckmann
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rose
authors.affiliation: District Hospital Loerrach, Medical Clinic, Loerrach, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Osterhues
authors.affiliation: Institute of Legal Medicine, University Hospital of Freiburg, Freiburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schmidt
authors.affiliation: Klinik für Innere Medizin, Cardiology Klinikum Ludwigsburg, Ludwigsburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wolpert
authors.affiliation: Medical Genetics, University Hospital Basel, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Miny
authors.affiliation: Center of Human Genetics and Laboratory Diagnostics, Martinsried, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Marschall
authors.affiliation: Department of Clinical Genetics, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Alders
authors.affiliation: Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: C R
authors.initials: CR
authors.lastname: Bezzina
authors.affiliation: Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia.
authors.forename: A A M
authors.initials: AAM
authors.lastname: Wilde
authors.affiliation: University Hospital Munich, Department of Medicine I, Ludwig Maximilians University, Munich, Germany; German Cardiovascular Research Center (DZHK), Partner Site: Munich Heart Alliance, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kääb
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Frankfurt am Main, Germany. Electronic address: kauferstein@em.uni-frankfurt.de.
authors.forename: S
authors.initials: S
authors.lastname: Kauferstein
mesh_terms: D000293:Adolescent; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: Brugada syndrome; Long QT syndrome; Promoter; SCN5A; Sudden death