title: Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
abstract: BACKGROUND
  Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited disorder typically caused by mutations in components of the cardiac desmosome. The prevalence and significance of desmosome mutations among patients with ARVD/C in North America have not been described previously. We report comprehensive desmosome genetic analysis for 100 North Americans with clinically confirmed or suspected ARVD/C.
  
  
  RESULTS
  In 82 individuals with ARVD/C and 18 people with suspected ARVD/C, DNA sequence analysis was performed on PKP2, DSG2, DSP, DSC2, and JUP. In those with ARVD/C, 52% harbored a desmosome mutation. A majority of these mutations occurred in PKP2. Notably, 3 of the individuals studied have a mutation in more than 1 gene. Patients with a desmosome mutation were more likely to have experienced ventricular tachycardia (73% versus 44%), and they presented at a younger age (33 versus 41 years) compared with those without a desmosome mutation. Men with ARVD/C were more likely than women to carry a desmosome mutation (63% versus 38%). A mutation was identified in 5 of 18 patients (28%) with suspected ARVD. In this smaller subgroup, there were no significant phenotypic differences identified between individuals with a desmosome mutation compared with those without a mutation.
  
  
  CONCLUSIONS
  Our study shows that in 52% of North Americans with ARVD/C a mutation in one of the cardiac desmosome genes can be identified. Compared with those without a desmosome gene mutation, individuals with a desmosome gene mutation had earlier-onset ARVD/C and were more likely to have ventricular tachycardia.
authors.affiliation: Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: A Dénise
authors.initials: AD
authors.lastname: den Haan
authors.forename: Boon Yew
authors.initials: BY
authors.lastname: Tan
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Zikusoka
authors.forename: Laura Ibañez
authors.initials: LI
authors.lastname: Lladó
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
authors.forename: Amy
authors.initials: A
authors.lastname: Daly
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.forename: Cynthia
authors.initials: C
authors.lastname: James
authors.forename: Nuria
authors.initials: N
authors.lastname: Amat-Alarcon
authors.forename: Theodore
authors.initials: T
authors.lastname: Abraham
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
authors.forename: Darshan
authors.initials: D
authors.lastname: Dalal
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D051187:Desmocollins / Q000737:chemistry / Q000235:genetics; D051301:Desmoglein 2 / Q000737:chemistry / Q000235:genetics; D051180:Desmoplakins / Q000737:chemistry / Q000235:genetics; D003896:Desmosomes / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009656:North America; D010375:Pedigree; D051191:Plakophilins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D055815:Young Adult; D051185:gamma Catenin
chemical_list: C081561:DSC2 protein, human; C495314:DSG2 protein, human; C495294:DSP protein, human; D051187:Desmocollins; D051301:Desmoglein 2; D051180:Desmoplakins; C495292:JUP protein, human; C495337:PKP2 protein, human; D051191:Plakophilins; D051185:gamma Catenin