Wattanasirichaigoon D, Beggs A H
Genetics Division, Children's Hospital, Boston, MA, USA.
Curr Opin Pediatr. 1998 Dec;10(6):628-34. doi: 10.1097/00008480-199810060-00016.
Recent discoveries of genes involved in long-QT syndrome (LQTS) have led to extensive progress in understanding the molecular basis for this disorder of syncope and sudden cardiac death secondary to ventricular arrhythmias. The emerging unifying theme is that all genes identified to date encode either structural or regulatory subunits for ion channels involved in cardiac repolarization. Defects have been identified in the KCNQ1, HERG, and KCNE1 genes, whose proteins form the K+ channels for the slowly and rapidly inwardly rectifying K+ currents IKs and IKr. Depending on their location and copy number, mutations of KCNQ1 and KCNE1 can cause either autosomal dominant Romano-Ward syndrome or autosomal recessive Jervell and Lange-Nielsen syndrome. The cardiac sodium channel gene, SCN5A, is also mutated in some Romano-Ward cases to produce defects in INa, the cardiac inward Na+ current. The fact that multiple genes are involved and that most LQTS mutations are "private" or "family-specific" complicates molecular diagnosis of LQTS which, currently, is limited to a small number of research laboratories. In future, genotypic determination of LQTS patients and their family members will hopefully lead to improved gene-specific prognostic determinations and therapeutic interventions.
近期对与长QT综合征（LQTS）相关基因的发现，在理解这种继发于室性心律失常的晕厥和心源性猝死疾病的分子基础方面取得了广泛进展。新出现的统一观点是，迄今为止鉴定出的所有基因均编码参与心脏复极化的离子通道的结构或调节亚基。已在KCNQ1、HERG和KCNE1基因中发现缺陷，其蛋白质形成用于缓慢和快速内向整流钾电流IKs和IKr的钾通道。根据其位置和拷贝数，KCNQ1和KCNE1的突变可导致常染色体显性遗传的 Romano-Ward综合征或常染色体隐性遗传的Jervell和Lange-Nielsen综合征。心脏钠通道基因SCN5A在一些Romano-Ward病例中也发生突变，导致心脏内向钠电流INa出现缺陷。多个基因参与以及大多数LQTS突变是“私人的”或“家族特异性的”这一事实，使LQTS的分子诊断变得复杂，目前该诊断仅限于少数研究实验室。未来，对LQTS患者及其家庭成员进行基因型测定有望带来改进的基因特异性预后判定和治疗干预。
