Awad Mark M, Dalal Darshan, Cho Eunpi, Amat-Alarcon Nuria, James Cynthia, Tichnell Crystal, Tucker April, Russell Stuart D, Bluemke David A, Dietz Harry C, Calkins Hugh, Judge Daniel P
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Am J Hum Genet. 2006 Jul;79(1):136-42. doi: 10.1086/504393. Epub 2006 Apr 28.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a disorder characterized by fibrofatty replacement of cardiac myocytes that typically manifests in the right ventricle. It is inherited as an autosomal dominant disease with reduced penetrance, although autosomal recessive forms of the disease also occur. We identified four probands with ARVD/C caused by mutations in DSG2, which encodes desmoglein-2, a component of the cardiac desmosome. No association between mutations in this gene and human disease has been reported elsewhere. One of these probands has compound-heterozygous mutations in DSG2, and the remaining three have isolated heterozygous missense mutations, each disrupting known functional components of desmoglein-2. We report that mutations in DSG2 contribute to the development of ARVD/C.
致心律失常性右室发育不良/心肌病（ARVD/C）是一种以心肌细胞纤维脂肪替代为特征的疾病，通常表现在右心室。它作为一种常染色体显性疾病遗传，外显率降低，不过也有常染色体隐性形式的该疾病。我们鉴定出四名由DSG2基因突变引起ARVD/C的先证者，DSG2编码桥粒芯糖蛋白-2，它是心脏桥粒的一个组成部分。该基因的突变与人类疾病之间的关联在其他地方尚未见报道。其中一名先证者在DSG2中有复合杂合突变，其余三名有孤立的杂合错义突变，每一个都破坏了桥粒芯糖蛋白-2已知的功能成分。我们报告DSG2中的突变促成了ARVD/C的发展。
