title: Age-dependent clinical and genetic characteristics in Japanese patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.
abstract: BACKGROUND
  Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease caused by desmosomal gene mutations, and presents as ventricular tachycardia and sudden cardiac death. Although the mean age at onset or diagnosis of ARVC/D are reported to be around the 30-40s, the age-dependent clinical and genetic differences remain unknown.
  
  
  RESULTS
  A total of 35 consecutive Japanese probands (23 male) who were clinically diagnosed with ARVC/D were enrolled in the present study, and genetic analysis of PKP2, DSP, DSG2, and DSC2 was done. The mean age at the first symptom and at diagnosis was 38.6±14.8 years and 40.5±17.7 years, respectively. Probands in whom the onset was cardiopulmonary arrest were significantly younger (22.3±15.3 years) than those with arrhythmia (41.1±13.2 years) or congestive heart failure (45.7±8.5 years). On genetic screening, 19 mutation carriers were identified. Although there was no age dependence for each gene mutation carrier, carriers with PKP2 premature stop codon developed the disease at a significantly younger age than other mutation carriers.
  
  
  CONCLUSIONS
  The initial clinical manifestations in some young probands were very severe, and PKP2 mutations with a premature stop codon would be associated with disease onset at a younger age.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu 520-2192, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.forename: Iori
authors.initials: I
authors.lastname: Nagaoka
authors.forename: Megumi
authors.initials: M
authors.lastname: Fukuyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kimura
authors.forename: Hideki
authors.initials: H
authors.lastname: Itoh
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shimizu
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000473:pathology; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D044466:Asian People; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism
chemical_list: C081561:DSC2 protein, human; C495314:DSG2 protein, human; C495294:DSP protein, human; D051187:Desmocollins; D051301:Desmoglein 2; D051180:Desmoplakins; C495337:PKP2 protein, human; D051191:Plakophilins