TY - JOUR
T1 - Desmoglein-2 and Desmocollin-2 Mutations in Dutch Arrhythmogenic Right Ventricular Dysplasia/Cardiomypathy Patients Results From a Multicenter Study
AU - Bhuiyan, Zahurul A.
AU - Jongbloed, Jan D. H.
AU - van der Smagt, Jasper
AU - Lombardi, Paola M.
AU - Wiesfeld, Ans C. P.
AU - Nelen, Marcel
AU - Schouten, Meyke
AU - Jongbloed, Roselie
AU - Cox, Moniek G. P. J.
AU - van Wolferen, Marleen
AU - Rodriguez, Luz M.
AU - van Gelder, Isabelle C.
AU - Bikker, Hennie
AU - Suurmeijer, Albert J. H.
AU - van den Berg, Maarten P.
AU - Mannens, Marcel M. A. M.
AU - Hauer, Richard N. W.
AU - Wilde, Arthur A. M.
AU - van Tintelen, J. Peter
PY - 2009
Y1 - 2009
N2 - 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. Methods and 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). (Circ Cardiovasc Genet. 2009;2:418-427.)
AB - 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. Methods and 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). (Circ Cardiovasc Genet. 2009;2:418-427.)
U2 - https://doi.org/10.1161/CIRCGENETICS.108.839829
DO - https://doi.org/10.1161/CIRCGENETICS.108.839829
M3 - Article
C2 - 20031616
SN - 1942-325X
VL - 2
SP - 418-U22
JO - Circulation. Cardiovascular genetics
JF - Circulation. Cardiovascular genetics
IS - 5
ER -