title: Role of novel DSP_p.Q986X genetic variation in arrhythmogenic right ventricular cardiomyopathy.
abstract: BACKGROUND
  Arrhythmogenic right ventricular cardiomyopathy is an inherited disease characterized by a progressive myocardium fibrofatty replacement. This abnormality disrupts electrical transmission causing ventricular arrhythmias and sudden cardiac death. This genetic disease is transmitted mainly with an autosomal dominant pattern. Our aim was to identify the genetic defect responsible for the pathology in a Spanish family, and to perform its phenotype connotations.
  
  
  METHODS
  A total of 15 individuals in a three-generation Spanish family were screened after the sudden cardiac death of one family member. All they underwent a complete physical examination, 12-lead electrocardiogram, 2-dimensional echocardiography, magnetic resonance imaging, exercise stress test, 24-h Holter and genetic testing.
  
  
  RESULTS
  Autopsy revealed the presence of biventricular arrhythmogenic dysplasia in deceased member. Six family members showed clinical symptoms but only three of them fulfilled definite diagnostic criteria of the disease. Genetic analysis showed a novel nonsense genetic variation in nine family members. All family members with clinical symptoms carried the genetic variation.
  
  
  CONCLUSIONS
  Genetic testing in families affected by arrhythmogenic right ventricular cardiomyopathy helps to identify the genetic cause responsible for the disease. The incomplete penetrance and variable phenotypic expression highlights the need of comprehensive genetic analysis and further phenotype implications of genetics to clarify the pathophysiology of the disease.
authors: Cardiovascular Genetics Center, UdG-IdIBGi, Girona, Spain.
authors: Oscar
authors: O
authors: Campuzano
authors: Mireia
authors: M
authors: Alcalde
authors: Paola
authors: P
authors: Berne
authors: Esther
authors: E
authors: Zorio
authors: Anna
authors: A
authors: Iglesias
authors: Josep
authors: J
authors: Navarro-Manchón
authors: Josep
authors: J
authors: Brugada
authors: Ramon
authors: R
authors: Brugada
mesh_terms: D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D051180:Desmoplakins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D010375:Pedigree; D014463:Ultrasonography
chemical_list: D018389:Codon, Nonsense; C495294:DSP protein, human; D051180:Desmoplakins
keywords: Arrhythmogenic right ventricular cardiomyopathy; Desmoplakin; Genetic testing; Sudden cardiac death