Syrris Petros, Ward Deirdre, Asimaki Angeliki, Evans Alison, Sen-Chowdhry Srijita, Hughes Sian E, McKenna William J
Department of Medicine, The Heart Hospital, University College London and University College London Hospitals Trust, 16-18 Westmoreland Street, London W1G 8PH, UK.
Eur Heart J. 2007 Mar;28(5):581-8. doi: 10.1093/eurheartj/ehl380. Epub 2006 Nov 14.
Mutations in the desmoglein-2 (DSG2) gene have been reported in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) but clinical information regarding the associated phenotype is at present limited. In this study, we aimed to clinically characterize probands and family members carrying a DSG2 mutation.
We investigated 86 Caucasian ARVC patients for mutations in DSG2 by direct sequencing and detected eight novel mutations in nine probands. Clinical evaluation of family members with DSG2 mutations demonstrated penetrance of 58% using Task Force criteria, or 75% using proposed modified criteria. Morphological abnormalities of the right ventricle were evident in 66% of gene carriers, left ventricular (LV) involvement in 25%, and classical right precordial T-wave inversion only in 26%. Sustained ventricular arrhythmia was present in 8% and a family history of sudden death/aborted sudden death in 66%.
Mutations in DSG2 display a high degree of penetrance. Disease expression was of variable severity with LV involvement a prominent feature. The low prevalence of classical ECG changes highlights the need to expand current diagnostic criteria to take account of LV disease, childhood disease expression, and incomplete penetrance.
致心律失常性右室心肌病（ARVC）患者中已报道有桥粒芯糖蛋白2（DSG2）基因突变，但目前关于相关表型的临床信息有限。在本研究中，我们旨在对携带DSG2突变的先证者及其家庭成员进行临床特征分析。
我们通过直接测序对86例白种人ARVC患者进行DSG2突变检测，在9例先证者中检测到8种新突变。对携带DSG2突变的家庭成员进行临床评估，采用工作组标准时外显率为58%，采用提议的改良标准时外显率为75%。66%的基因携带者右心室有形态学异常，25%有左心室（LV）受累，仅26%有典型的右胸前导联T波倒置。8%有持续性室性心律失常，66%有猝死/未遂猝死家族史。
DSG2突变显示出高度的外显率。疾病表现严重程度不一，LV受累是突出特征。经典心电图改变的低发生率凸显了扩大当前诊断标准以考虑LV疾病、儿童期疾病表现和不完全外显率的必要性。
