title: Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study.
abstract: BACKGROUND
  This study aimed to evaluate the prevalence and type of mutations in the major desmosomal genes, Plakophilin-2 (PKP2), Desmoglein-2 (DSG2), and Desmocollin-2 (DSC2), in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. We also aimed to distinguish relevant clinical and ECG parameters.
  
  
  RESULTS
  Clinical evaluation was performed according to the Task Force Criteria (TFC). We analyzed the genes in (a) 57 patients who fulfilled the ARVD/C TFC (TFC+), (b) 28 patients with probable ARVD/C (1 major and 1 minor, or 3 minor criteria), and (c) 31 patients with 2 minor or 1 major criteria. In the TFC+ ARVD/C group, 23 patients (40%) had PKP2 mutations, 4 (7%) had DSG2 mutations, and 1 patient (2%) carried a mutation in DSC2, whereas 1 patient (2%) had a mutation in both DSG2 and DSC2. Among the DSG2 and DSC2 mutation-positive TFC+ ARVD/C probands, 2 carried compound heterozygous mutations and 1 had digenic mutations. In probable ARVD/C patients and those with 2 minor or 1 major criteria for ARVD/C, mutations were less frequent and they were all heterozygous. Negative T waves in the precordial leads were observed more (P<0.002) among mutation carriers than noncarriers and in particular in PKP2 mutation carriers.
  
  
  CONCLUSIONS
  Mutations in DSG2 and DSC2 are together less prevalent (10%) than PKP2 mutations (40%) in Dutch TFC+ ARVD/C patients. Interestingly, biallelic or digenic DSC2 and/or DSG2 mutations are frequently identified in TFC+ ARVD/C patients, suggesting that a single mutation is less likely to cause a full-blown ARVD/C phenotype. Negative T waves on ECG were prevalent among mutation carriers (P<0.002).
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. z.a.Bhuiyan@amc.uva.nl
authors.forename: Zahurul A
authors.initials: ZA
authors.lastname: Bhuiyan
authors.forename: Jan D H
authors.initials: JD
authors.lastname: Jongbloed
authors.forename: Jasper
authors.initials: J
authors.lastname: van der Smagt
authors.forename: Paola M
authors.initials: PM
authors.lastname: Lombardi
authors.forename: Ans C P
authors.initials: AC
authors.lastname: Wiesfeld
authors.forename: Marcel
authors.initials: M
authors.lastname: Nelen
authors.forename: Meyke
authors.initials: M
authors.lastname: Schouten
authors.forename: Roselie
authors.initials: R
authors.lastname: Jongbloed
authors.forename: Moniek G P J
authors.initials: MG
authors.lastname: Cox
authors.forename: Marleen
authors.initials: M
authors.lastname: van Wolferen
authors.forename: Luz M
authors.initials: LM
authors.lastname: Rodriguez
authors.forename: Isabelle C
authors.initials: IC
authors.lastname: van Gelder
authors.forename: Hennie
authors.initials: H
authors.lastname: Bikker
authors.forename: Albert J H
authors.initials: AJ
authors.lastname: Suurmeijer
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Marcel M A M
authors.initials: MM
authors.lastname: Mannens
authors.forename: Richard N W
authors.initials: RN
authors.lastname: Hauer
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
mesh_terms: D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D051187:Desmocollins / Q000235:genetics* / Q000378:metabolism; D051301:Desmoglein 2 / Q000235:genetics* / Q000378:metabolism; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C081561:DSC2 protein, human; C495314:DSG2 protein, human; D051187:Desmocollins; D051301:Desmoglein 2; C495337:PKP2 protein, human; D051191:Plakophilins