title: Desmoplakin truncations and arrhythmogenic left ventricular cardiomyopathy: characterizing a phenotype.
abstract: OBJECTIVE
  Risk stratification for sudden death in arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging in clinical practice. We lack recommendations for the risk stratification of exclusive left-sided phenotypes. The aim of this study was to investigate genotype-phenotype correlations in patients carrying a novel DSP c.1339C>T, and to review the literature on the clinical expression and the outcomes in patients with DSP truncating mutations.
  
  
  RESULTS
  Genetic screening of the DSP gene was performed in 47 consecutive patients with a phenotype of either an ARVC (n = 24) or an idiopathic dilated cardiomyopathy (DCM), who presented with ventricular arrhythmias or a family history of sudden death (n = 23) (aged 40 ± 19 years, 62% males). Three unrelated probands with DCM were found to be carriers of a novel mutation (c.1339C>T). Cascade family screening led to the identification of 15 relatives who are carriers. Penetrance in c.1339C>T carriers was 83%. Sustained ventricular tachycardia was the first clinical manifestation in six patients and nine patients were diagnosed with left ventricular impairment (two had overt severe disease and seven had a mild dysfunction). Cardiac magnetic resonance revealed left ventricular involvement in nine cases and biventricular disease in three patients. Extensive fibrotic patterns in six and non-compaction phenotype in five patients were the hallmark in imaging.
  
  
  CONCLUSIONS
  DSP c.1339C>T is associated with an aggressive clinical phenotype of left-dominant arrhythmogenic cardiomyopathy and left ventricular non-compaction. Truncating mutations in desmoplakin are consistently associated with aggressive phenotypes and must be considered as a risk factor of sudden death. Since ventricular tachycardia occurs even in the absence of severe systolic dysfunction, an implantable cardioverter-defibrillator should be indicated promptly.
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Jose María
authors.initials: JM
authors.lastname: López-Ayala
authors.affiliation: Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gómez-Milanés
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Sánchez Muñoz
authors.affiliation: Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Espejo
authors.affiliation: A Coruña University Hospital, A Coruña Biomedical Research Institute, A Coruña, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Ortíz
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: González-Carrillo
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: López-Cuenca
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Oliva-Sandoval
authors.affiliation: A Coruña University Hospital, A Coruña Biomedical Research Institute, A Coruña, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
authors.affiliation: Department of Cardiology, University of Murcia, Virgen de la Arrixaca University Hospital, Murcia, Spain jgimeno@secardiologia.es.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gimeno
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000453:epidemiology* / Q000235:genetics*; D051180:Desmoplakins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D051180:Desmoplakins
keywords: Arrhythmogenic cardiomyopathy; Desmoplakin; Dilated cardiomyopathy; Implantable cardioverter-defibrillator; Sudden death