Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Am J Cardiol. 2013 Oct 15;112(8):1197-206. doi: 10.1016/j.amjcard.2013.06.017. Epub 2013 Jul 19.
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.
致心律失常性右室心肌病/发育不良（ARVD/C）常与桥粒蛋白基因突变相关，但也可能与非桥粒蛋白基因突变相关。本研究旨在根据 2010 年修订的工作组标准（TFC）评估磷酸化酶磷蛋白（PLN）基因突变对 ARVD/C 诊断的贡献。在 142 例经证实的 ARVD/C 荷兰患者（106 例男性，平均年龄 51±13 岁）中，检测了 5 个已知的桥粒蛋白基因（PKP2、DSP、DSC2、DSG2 和 JUP）和非桥粒蛋白 PLN 基因。在进行基因分析后，比较了桥粒蛋白突变携带者和 PLN 突变携带者的表型特征。在 142 例 ARVD/C 患者中（42%），59 例未发现桥粒蛋白突变。在 142 例患者中（13%），发现了 PLN 种系突变 c.40_42delAGA（p.Arg14del）。PLN 突变携带者更常出现低电压心电图（p=0.004）、V4 至 V6 导联的 T 波倒置（p<0.001）以及额外的结构性（p=0.007）或功能性（p=0.017）左心室损害，而桥粒蛋白突变携带者更常出现单一的右心室异常。修订后的 TFC 纳入了 142 例经证实的 ARVD/C 患者中的 21 例，这些患者不符合 1994 年 TFC，其中包括 7 例 PLN 突变携带者。总之，PLN 突变对 2010 年 TFC 诊断的 ARVD/C 有很大贡献。在 59 例遗传原因不明的 ARVD/C 患者中（32%）发现了这种非桥粒蛋白突变。PLN 突变携带者具有 ARVD/C 的特征，包括重要的右心室受累，以及更常出现低电压心电图、左胸前导联 T 波倒置和左心室受累。
