Leon H. Charney Division of Cardiology, Grossman School of Medicine, New York University, New York, NY, USA; email:
Department of Internal Medicine, Kantonsspital Baden, Baden, Switzerland.
Annu Rev Genomics Hum Genet. 2022 Aug 31;23:255-274. doi: 10.1146/annurev-genom-112921-011200. Epub 2022 May 13.
Brugada syndrome is a heritable channelopathy characterized by a peculiar electrocardiogram (ECG) pattern and increased risk of cardiac arrhythmias and sudden death. The arrhythmias originate because of an imbalance between the repolarizing and depolarizing currents that modulate the cardiac action potential. Even if an overt structural cardiomyopathy is not typical of Brugada syndrome, fibrosis and structural changes in the right ventricle contribute to a conduction slowing, which ultimately facilitates ventricular arrhythmias. Currently, Mendelian autosomal dominant transmission is detected in less than 25% of all clinical confirmed cases. Although 23 genes have been associated with the condition, only , encoding the cardiac sodium channel, is considered clinically actionable and disease causing. The limited monogenic inheritance has pointed toward new perspectives on the possible complex genetic architecture of the disease, involving polygenic inheritance and a polygenic risk score that can influence penetrance and risk stratification.
Brugada 综合征是一种遗传性离子通道病，其特征为心电图（ECG）模式特殊，心律失常和心脏性猝死风险增加。心律失常的起源是由于调节心脏动作电位的去极化和复极化电流之间的失衡。即使 Brugada 综合征并不典型，但右心室纤维化和结构改变导致传导减慢，最终促进室性心律失常。目前，孟德尔常染色体显性遗传在所有临床确诊病例中不到 25%。尽管已经有 23 个基因与该疾病相关，但只有编码心脏钠离子通道的基因被认为具有临床可操作性和致病作用。有限的单基因遗传促使人们对该疾病可能的复杂遗传结构有了新的认识，包括多基因遗传和多基因风险评分，这些因素可能影响外显率和风险分层。
