Desmoglein-2 and Desmocollin-2 Mutations in Dutch Arrhythmogenic Right Ventricular Dysplasia/Cardiomypathy Patients Results From a Multicenter Study

被引:75
作者
Bhuiyan, Zahurul A. [1 ]
Jongbloed, Jan D. H. [3 ]
van der Smagt, Jasper [6 ]
Lombardi, Paola M. [1 ]
Wiesfeld, Ans C. P. [4 ]
Nelen, Marcel [6 ]
Schouten, Meyke [8 ]
Jongbloed, Roselie [8 ]
Cox, Moniek G. P. J. [7 ,10 ]
van Wolferen, Marleen [3 ]
Rodriguez, Luz M. [9 ]
van Gelder, Isabelle C. [4 ,10 ]
Bikker, Hennie [1 ]
Suurmeijer, Albert J. H. [5 ]
van den Berg, Maarten P. [4 ,10 ]
Mannens, Marcel M. A. M. [1 ]
Hauer, Richard N. W. [7 ,10 ]
Wilde, Arthur A. M. [2 ,10 ]
van Tintelen, J. Peter [3 ,10 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 AB Groningen, Netherlands
[4] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands
[5] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, NL-9700 AB Groningen, Netherlands
[6] Univ Med Ctr Utrecht, Dept Clin Genet, Utrecht, Netherlands
[7] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands
[8] Univ Maastricht, Dept Clin Genet, Maastricht, Netherlands
[9] Univ Maastricht, Dept Cardiol, Maastricht, Netherlands
[10] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands
关键词
arrhythmia; cardiomyopathy; desmosomes; genetics; PLAKOPHILIN-2; MUTATIONS; MISSENSE MUTATIONS; PLAKOGLOBIN CAUSES; NAXOS-DISEASE; CARDIOMYOPATHY; GENE; EXPRESSION; DYSPLASIA; FAMILIES; SPECTRUM;
D O I
10.1161/CIRCGENETICS.108.839829
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.)
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收藏
页码:418 / U22
页数:12
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