den Haan A Dénise, Tan Boon Yew, Zikusoka Michelle N, Lladó Laura Ibañez, Jain Rahul, Daly Amy, Tichnell Crystal, James Cynthia, Amat-Alarcon Nuria, Abraham Theodore, Russell Stuart D, Bluemke David A, Calkins Hugh, Dalal Darshan, Judge Daniel P
Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Circ Cardiovasc Genet. 2009 Oct;2(5):428-35. doi: 10.1161/CIRCGENETICS.109.858217. Epub 2009 Jun 3.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited disorder typically caused by mutations in components of the cardiac desmosome. The prevalence and significance of desmosome mutations among patients with ARVD/C in North America have not been described previously. We report comprehensive desmosome genetic analysis for 100 North Americans with clinically confirmed or suspected ARVD/C.
In 82 individuals with ARVD/C and 18 people with suspected ARVD/C, DNA sequence analysis was performed on PKP2, DSG2, DSP, DSC2, and JUP. In those with ARVD/C, 52% harbored a desmosome mutation. A majority of these mutations occurred in PKP2. Notably, 3 of the individuals studied have a mutation in more than 1 gene. Patients with a desmosome mutation were more likely to have experienced ventricular tachycardia (73% versus 44%), and they presented at a younger age (33 versus 41 years) compared with those without a desmosome mutation. Men with ARVD/C were more likely than women to carry a desmosome mutation (63% versus 38%). A mutation was identified in 5 of 18 patients (28%) with suspected ARVD. In this smaller subgroup, there were no significant phenotypic differences identified between individuals with a desmosome mutation compared with those without a mutation.
Our study shows that in 52% of North Americans with ARVD/C a mutation in one of the cardiac desmosome genes can be identified. Compared with those without a desmosome gene mutation, individuals with a desmosome gene mutation had earlier-onset ARVD/C and were more likely to have ventricular tachycardia.
致心律失常性右心室发育不良/心肌病（ARVD/C）是一种遗传性疾病，通常由心脏桥粒成分的突变引起。此前尚未描述北美ARVD/C患者中桥粒突变的患病率和意义。我们报告了对100名临床确诊或疑似ARVD/C的北美人进行的全面桥粒基因分析。
对82例ARVD/C患者和18例疑似ARVD/C患者的PKP2、DSG2、DSP、DSC2和JUP进行了DNA序列分析。在ARVD/C患者中，52%携带桥粒突变。这些突变大多发生在PKP2基因。值得注意的是，3名研究对象的突变发生在不止一个基因中。与无桥粒突变的患者相比，有桥粒突变的患者更易发生室性心动过速（73%对44%），且发病年龄更小（33岁对41岁）。ARVD/C男性携带桥粒突变的可能性高于女性（63%对38%）。在18例疑似ARVD患者中有5例（28%）检测到突变。在这个较小的亚组中，有桥粒突变的个体与无突变的个体之间未发现明显的表型差异。
我们的研究表明，在52%的北美ARVD/C患者中可鉴定出心脏桥粒基因之一的突变。与无桥粒基因突变的个体相比，有桥粒基因突变的个体ARVD/C发病更早，且更易发生室性心动过速。
