title: Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy.
abstract: OBJECTIVE
  To investigate whether phospholamban gene (PLN) mutations underlie patients diagnosed with either arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic dilated cardiomyopathy (DCM).
  
  
  RESULTS
  We screened a cohort of 97 ARVC and 257 DCM unrelated index patients for PLN mutations and evaluated their clinical characteristics. PLN mutation R14del was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. Haplotype analysis revealed a common founder, estimated to be between 575 and 825 years old. A low voltage electrocardiogram was present in 46 % of R14del carriers. Compared with R14del- DCM patients, R14del+ DCM patients more often demonstrated appropriate implantable cardioverter defibrillator discharge (47 % vs. 10 % , P < 0.001), cardiac transplantation (18 % vs. 2 % , P < 0.001), and a family history for sudden cardiac death (SCD) at < 50 years (36 % vs. 16 % , P = 0.007). We observed a similar pattern in the ARVC patients although this was not statistically significant. The average age of 26 family members who died of SCD was 37.7 years. Immunohistochemistry in available myocardial samples revealed absent/depressed plakoglobin levels at intercalated disks in five of seven (71 %) R14del+ ARVC samples, but in only one of nine (11 %) R14del+ DCM samples (P = 0.03).
  
  
  CONCLUSIONS
  The PLN R14del founder mutation is present in a substantial number of patients clinically diagnosed with DCM or ARVC. R14del+ patients diagnosed with DCM showed an arrhythmogenic phenotype, and SCD at young age can be the presenting symptom. These findings support the concept of 'arrhythmogenic cardiomyopathy'.
authors: Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
authors: Paul A
authors: PA
authors: van der Zwaag
authors: Ingrid A W
authors: IA
authors: van Rijsingen
authors: Angeliki
authors: A
authors: Asimaki
authors: Jan D H
authors: JD
authors: Jongbloed
authors: Dirk J
authors: DJ
authors: van Veldhuisen
authors: Ans C P
authors: AC
authors: Wiesfeld
authors: Moniek G P J
authors: MG
authors: Cox
authors: Laura T
authors: LT
authors: van Lochem
authors: Rudolf A
authors: RA
authors: de Boer
authors: Robert M W
authors: RM
authors: Hofstra
authors: Imke
authors: I
authors: Christiaans
authors: Karin Y
authors: KY
authors: van Spaendonck-Zwarts
authors: Ronald H
authors: RH
authors: Lekanne dit Deprez
authors: Daniel P
authors: DP
authors: Judge
authors: Hugh
authors: H
authors: Calkins
authors: Albert J H
authors: AJ
authors: Suurmeijer
authors: Richard N W
authors: RN
authors: Hauer
authors: Jeffrey E
authors: JE
authors: Saffitz
authors: Arthur A M
authors: AA
authors: Wilde
authors: Maarten P
authors: MP
authors: van den Berg
authors: J Peter
authors: JP
authors: van Tintelen
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D016757:Death, Sudden, Cardiac; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D013223:Statistics as Topic; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000099211:Phospholamban