Electrocardiographic prediction of abnormal genotype in congenital long QT syndrome: Experience in 101 related family members
Electrocardiographic prediction of abnormal genotype in congenital long QT syndrome: Experience in 101 related family members
复制标题
DOI：
10.1046/j.1540-8167.2001.00455.x
复制
发表时间：
2001-04-01
影响因子：
2.7
通讯作者：
Brown, AM
中科院分区：
文献类型：
--
作者：
Kaufman, ES;Priori, SG;Brown, AM
导读：以往的研究表明先天性长QT综合征（LQTS）由于外显率的变化和遗传异质性，尤其是当来自多个具有不同突变的家庭的受试者合并时，诊断困难。我们假设结合临床和心电图技术可以识别单个先天性LQTS家族的基因携带者。方法和结果：对一个LQTS家族的101名基因分型成员进行了病史和心电图分析，其中包括26名HERG突变携带者。48名家庭成员也接受了QT和T波交替（TWA）分析和24小时动态心电图监测（QT和心率变异性分析）的运动试验。包括年龄、性别、QTc和按年龄划分的QTc的逻辑回归模型提供了基因携带者状态的最佳预测，尽管在有和没有突变的受试者中QTc存在大量重叠（78%）。QTc对13岁以下儿童没有帮助。TWA（很少观察到）并没有显著增加模型预测异常基因型的能力。结论：即使在这种同质的LQTS人群中，表型也是如此多变，以至于临床和详细的ECG分析不能准确诊断基因携带者状态，特别是在儿童中。持续微伏TWA是LQTS的特异性标记（100%），但不敏感（18%）。其预测该人群心律失常风险的能力仍有待确定。基因检测在筛选LQTS携带者中起着重要作用。
Introduction: Previous studies showed that diagnosing congenital long QT syndrome (LQTS) is difficult due to variable penetrance and genetic heterogeneity, especially when subjects from multiple families with diverse mutations are combined. We hypothesized that a combination of clinical and ECG techniques could identify gene carriers within a single family with congenital LQTS,Methods and Results: One hundred one genotyped members of a family with LQTS, including 26 carriers of a HERG mutation, underwent history and ECG analysis. Forty-eight family members also underwent exercise testing with QT and T wave alternans (TWA) analysis and 24-hour Holter monitoring with QT and heart rate variability analysis. A logistic regression model, which included age, gender, QTc, and QTc by age, provided the best prediction of gene carrier status, although there was substantial overlap (78%) of QTc among subjects with and without the mutation. QTc was not helpful as a discriminator in children less than or equal to 13 years. TWA (observed infrequently) did not add significantly to the model's ability to predict abnormal genotype,Conclusion: Even in this homogeneous LQTS population, the phenotype was so variable that clinical and detailed ECG analyses did not permit an accurate diagnosis of gene carrier status, especially in children. Sustained microvolt TWA was a specific (100%) but insensitive (18%) marker for LQTS. Its ability to predict risk of arrhythmia in this population remains to be determined. Genetic testing serves an essential role in screening for carriers of LQTS.