TY - JOUR
T1 - Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy
T2 - Evidence supporting the concept of arrhythmogenic cardiomyopathy
AU - Van Der Zwaag, Paul A.
AU - Van Rijsingen, Ingrid A.W.
AU - Asimaki, Angeliki
AU - Jongbloed, Jan D.H.
AU - Van Veldhuisen, Dirk J.
AU - Wiesfeld, Ans C.P.
AU - Cox, Moniek G.P.J.
AU - Van Lochem, Laura T.
AU - De Boer, Rudolf A.
AU - Hofstra, Robert M.W.
AU - Christiaans, Imke
AU - Van Spaendonck-Zwarts, Karin Y.
AU - Deprez, Ronald H.Lekanne Dit
AU - Judge, Daniel P.
AU - Calkins, Hugh
AU - Suurmeijer, Albert J.H.
AU - Hauer, Richard N.W.
AU - Saffitz, Jeffrey E.
AU - Wilde, Arthur A.M.
AU - Van Den Berg, Maarten P.
AU - Van Tintelen, J. Peter
PY - 2012/11
Y1 - 2012/11
N2 - Aims To investigate whether phospholamban gene (PLN) mutations underlie patients diagnosed with either arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic dilated cardiomyopathy (DCM).Methods and resultsWe 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).ConclusionsThe 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'.
AB - Aims To investigate whether phospholamban gene (PLN) mutations underlie patients diagnosed with either arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic dilated cardiomyopathy (DCM).Methods and resultsWe 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).ConclusionsThe 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'.
KW - Arrhythmia
KW - Arrhythmogenic cardiomyopathy
KW - Arrhythmogenic right ventricular cardiomyopathy
KW - Dilated cardiomyopathy
KW - Genetics
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U2 - 10.1093/eurjhf/hfs119
DO - 10.1093/eurjhf/hfs119
M3 - Article
C2 - 22820313
AN - SCOPUS:84867736080
SN - 1388-9842
VL - 14
SP - 1199
EP - 1207
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 11
ER -