Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is one of the leading causes of sudden cardiac death. Recent studies have shown that ARVC, which is an inheritable genetic change, results from mutat...Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is one of the leading causes of sudden cardiac death. Recent studies have shown that ARVC, which is an inheritable genetic change, results from mutations in genes encoding desmosomal proteins. Plakophilin-2 is an important component of the desmosome. Because the full range of genetic variations related to ARVC is unknown and no related studies of the Chinese population have been reported, we aimed to investigate the genetic variation of plakophilin-2 in ARVC patients from the Southern Region of China. Methods Genomic DNA was isolated from peripheral blood samples of all 34 ARVC patients, who were screened through a clinical evaluation. They were used to detect variations in the sequences of the plakophilin-2 genes by polymerase chain reaction amplification in combination with direct sequencing. Results In exon-1 of the plakophilin-2 gene, a deletion mutation （c.145_148 del GACA） was found in one family pedigree. The mutation was also found in exon-2, 4, and 11 of the plakophilin-2 gene. The QT interval dispersion of the ECG was considerably longer in the mutation group than in the non-mutation group of ARVC patients, and this result was statistically significant （P 〈0.05）. Conclusion We discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese ARVC population.展开更多
Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC populatio...Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. Methods A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. Results Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in nondesmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them （one of each gene） appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. Conclusions Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Nondesmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.展开更多
随着对致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)研究的进展,目前已不再认为ARVC只是桥粒蛋白基因突变引起的一种累及右室的遗传性心肌病。ARVC可以由非桥粒蛋白的多种基因突变或非遗传因素引起,...随着对致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)研究的进展,目前已不再认为ARVC只是桥粒蛋白基因突变引起的一种累及右室的遗传性心肌病。ARVC可以由非桥粒蛋白的多种基因突变或非遗传因素引起,并且可以首先累及左室。因此,2019年制定ARVC诊断标准的国际专家组提出了该病的新的临床分型,并对2010年的诊断标准作出了新的评价。本文就ARVC的临床分型、致病基因、诊断及治疗研究进展等方面进行综述。展开更多
目的:探究超声心动图联合心电图对致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)的诊断价值,为疾病诊断及治疗方案的制订提供依据。方法:选取2015年9月至2017年10月经心内膜活检证实的39例ARVC患者作...目的:探究超声心动图联合心电图对致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)的诊断价值,为疾病诊断及治疗方案的制订提供依据。方法:选取2015年9月至2017年10月经心内膜活检证实的39例ARVC患者作为研究对象,均行超声心动图与心电图检查,对超声心动图与心电图的主要表现进行统计分析,并比较超声心动图联合心电图诊断与超声心动图、心电图单一方法诊断ARVC的阳性率。结果:超声心动图主要表现为右室增大(89.74%)、右室肌小梁紊乱(76.92%)、右室流出道增宽(66.67%)、右室壁弥漫性变薄(66.67%)、右房增大(51.28%)等;心电图主要表现为V1~V3导联QRS波增宽超过110 ms(69.23%)、V1~V3导联T波倒置(61.54%)、出现Epsilon波(35.90%)。应用超声心动图联合心电图诊断的阳性率为89.74%,均高于心电图(阳性率66.67%)、超声心动图(阳性率30.77%)单一诊断,差异有统计学意义(P<0.05)。结论:超声心动图联合心电图诊断可明显提高ARVC诊断阳性率,减少漏诊,为临床制订早期防治方案提供可靠依据。展开更多
文摘Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is one of the leading causes of sudden cardiac death. Recent studies have shown that ARVC, which is an inheritable genetic change, results from mutations in genes encoding desmosomal proteins. Plakophilin-2 is an important component of the desmosome. Because the full range of genetic variations related to ARVC is unknown and no related studies of the Chinese population have been reported, we aimed to investigate the genetic variation of plakophilin-2 in ARVC patients from the Southern Region of China. Methods Genomic DNA was isolated from peripheral blood samples of all 34 ARVC patients, who were screened through a clinical evaluation. They were used to detect variations in the sequences of the plakophilin-2 genes by polymerase chain reaction amplification in combination with direct sequencing. Results In exon-1 of the plakophilin-2 gene, a deletion mutation （c.145_148 del GACA） was found in one family pedigree. The mutation was also found in exon-2, 4, and 11 of the plakophilin-2 gene. The QT interval dispersion of the ECG was considerably longer in the mutation group than in the non-mutation group of ARVC patients, and this result was statistically significant （P 〈0.05）. Conclusion We discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese ARVC population.
文摘Background Arrhythmogenic right ventricular cardiomyopathy （ARVC） is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. Methods A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. Results Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in nondesmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them （one of each gene） appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. Conclusions Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Nondesmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.
文摘随着对致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)研究的进展,目前已不再认为ARVC只是桥粒蛋白基因突变引起的一种累及右室的遗传性心肌病。ARVC可以由非桥粒蛋白的多种基因突变或非遗传因素引起,并且可以首先累及左室。因此,2019年制定ARVC诊断标准的国际专家组提出了该病的新的临床分型,并对2010年的诊断标准作出了新的评价。本文就ARVC的临床分型、致病基因、诊断及治疗研究进展等方面进行综述。
文摘目的:探究超声心动图联合心电图对致心律失常性右室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)的诊断价值,为疾病诊断及治疗方案的制订提供依据。方法:选取2015年9月至2017年10月经心内膜活检证实的39例ARVC患者作为研究对象,均行超声心动图与心电图检查,对超声心动图与心电图的主要表现进行统计分析,并比较超声心动图联合心电图诊断与超声心动图、心电图单一方法诊断ARVC的阳性率。结果:超声心动图主要表现为右室增大(89.74%)、右室肌小梁紊乱(76.92%)、右室流出道增宽(66.67%)、右室壁弥漫性变薄(66.67%)、右房增大(51.28%)等;心电图主要表现为V1~V3导联QRS波增宽超过110 ms(69.23%)、V1~V3导联T波倒置(61.54%)、出现Epsilon波(35.90%)。应用超声心动图联合心电图诊断的阳性率为89.74%,均高于心电图(阳性率66.67%)、超声心动图(阳性率30.77%)单一诊断,差异有统计学意义(P<0.05)。结论:超声心动图联合心电图诊断可明显提高ARVC诊断阳性率,减少漏诊,为临床制订早期防治方案提供可靠依据。
