Desmoglein-2 and Desmocollin-2 Mutations in Dutch Arrhythmogenic Right Ventricular Dysplasia/Cardiomypathy Patients Results From a Multicenter Study
Desmoglein-2 and Desmocollin-2 Mutations in Dutch Arrhythmogenic Right Ventricular Dysplasia/Cardiomypathy Patients Results From a Multicenter Study
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DOI：
10.1161/circgenetics.108.839829
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发表时间：
2009-10-01
影响因子：
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通讯作者：
van Tintelen, J. Peter
中科院分区：
文献类型：
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作者：
Bhuiyan, Zahurul A.;Jongbloed, Jan D. H.;van Tintelen, J. Peter
背景-本研究旨在评估致心律失常性右心室发育不良/心肌病（ARVD/C）患者中主要桥粒基因Plakophilin-2（PKP 2）、桥粒芯糖蛋白-2（DSG 2）和桥粒胶原蛋白-2（DSC 2）突变的发生率和类型。我们还旨在区分相关的临床和心电图parameters.Methods和结果进行临床评价，根据工作组标准（TFC）。我们分析了（a）57例符合ARVD/C TFC（TFC+）的患者，（B）28例可能患有ARVD/C的患者（1例严重和1例轻微，或3例轻微标准）和（c）31例符合2项轻微或1项主要标准的患者的基因。在TFC+ ARVD/C组中，23例患者（40%）有PKP 2突变，4例患者（7%）有DSG 2突变，1例患者（2%）有DSC 2突变，而1例患者（2%）有DSG 2和DSC 2突变。在DSG 2和DSC 2突变阳性的TFC+ ARVD/C先证者中，2例携带复合杂合突变，1例携带双基因突变。在很可能的ARVD/C患者和有2个次要或1个主要ARVD/C标准的患者中，突变频率较低，且均为杂合子。在突变携带者中观察到的胸导联负T波多于非携带者（P < 0.002），尤其是PKP 2突变携带者。结论：在荷兰TFC+ ARVD/C患者中，DSG 2和DSC 2突变的发生率（10%）低于PKP 2突变（40%）。有趣的是，在TFC+ ARVD/C患者中经常发现双等位基因或双基因DSC 2和/或DSG 2突变，这表明单个突变不太可能导致完全的ARVD/C表型。突变携带者心电图负T波多见（P < 0.002）。(Circ Genet. 2009;2：418-427）。
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.)