Hedley Paula L, Durrheim Glenda A, Hendricks Firzana, Goosen Althea, Jespersgaard Cathrine, Støvring Birgitte, Pham Tam T, Christiansen Michael, Brink Paul A, Corfield Valerie A
US/MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, South Africa.
Cardiovasc J Afr. 2013 Jul;24(6):231-7. doi: 10.5830/CVJA-2013-032.
Congenital long QT syndrome (cLQTS) is a genetic disorder predisposing to ventricular arrhythmia, syncope and sudden death. Over 700 different cLQTS-causing mutations in 13 genes are known. The genetic spectrum of LQTS in 44 South African cLQTS patients (23 known to carry the South African founder mutation p.A341V in KCNQ1) was established by screening for mutations in the coding regions of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A, the most frequently implicated cLQTS-causing genes (five-gene screening). Fourteen disease-causing mutations were identified, eight (including the founder mutation) in KCNQ1, five in KCNH2 and one in KCNE1. Two mutations were novel. Two double heterozygotes were found among the 23 families (8.5%) carrying the founder mutation. In conclusion, cLQTS in South Africa reflects both a strong founder effect and a genetic spectrum similar to that seen in other populations. Consequently, five-gene screening should be offered as a standard screening option, as is the case internationally. This will disclose compound and double heterozygotes. Fivegene screening will most likely be even more informative in other South African sub-populations with a greater genetic diversity.
先天性长QT综合征（cLQTS）是一种遗传性疾病，易引发室性心律失常、晕厥和猝死。已知有13个基因中存在700多种不同的导致cLQTS的突变。通过对KCNQ1、KCNH2、KCNE1、KCNE2和SCN5A这几个最常涉及的导致cLQTS的基因（五基因筛查）的编码区进行突变筛查，确定了44例南非cLQTS患者（其中23例已知携带KCNQ1基因中的南非始祖突变p.A341V）的LQTS遗传谱。共鉴定出14个致病突变，其中8个（包括始祖突变）在KCNQ1基因中，5个在KCNH2基因中，1个在KCNE1基因中。有两个突变是新发现的。在携带始祖突变的23个家族中发现了2例双杂合子（8.5%）。总之，南非的cLQTS既反映了强烈的始祖效应，也反映了与其他人群相似的遗传谱。因此，应像国际上那样，将五基因筛查作为标准筛查选项。这将揭示复合杂合子和双杂合子。在遗传多样性更高的其他南非亚人群中，五基因筛查可能会提供更多信息。
