Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently 
associated with desmosomal mutations. However, nondesmosomal mutations may be 
involved. The aim of this study was to assess the contribution of a 
phospholamban (PLN) gene mutation to ARVD/C diagnosis according to the revised 
2010 task force criteria (TFC). In 142 Dutch patients (106 men, mean age 51 ± 13 
years) with proven ARVD/C (fulfillment of 2010 TFC for diagnosis), 5 known 
desmosomal genes (PKP2, DSP, DSC2, DSG2, and JUP) and the nondesmosomal PLN gene 
were screened. After genetic analysis, phenotypic characteristics of desmosomal 
versus PLN mutation carriers were compared. In 59 of 142 patients with ARVD/C 
(42%), no desmosomal mutation was found. In 19 of 142 patients (13%), the PLN 
founder mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation 
carriers more often had low-voltage electrocardiograms (p = 0.004), inverted T 
waves in leads V4 to V6 (p <0.001), and additional structural (p = 0.007) or 
functional (p = 0.017) left ventricular impairment, whereas desmosomal mutation 
carriers had more solitary right ventricular abnormalities. The revised TFC 
included 21 of 142 patients with proven ARVD/C who did not meet the 1994 TFC, 
including 7 PLN mutation carriers. In conclusion, there is a substantial 
contribution of PLN mutation to ARVD/C diagnosis by the 2010 TFC. In 32% of 
patients (19 of 59) with genetically unexplained proven ARVD/C, this 
nondesmosomal mutation was found. PLN mutation carriers have ARVD/C 
characteristics, including important right ventricular involvement, and 
additionally more often low-voltage electrocardiograms, inverted T waves in the 
left precordial leads, and left ventricular involvement.