Moss A J, Zareba W, Benhorin J, Locati E H, Hall W J, Robinson J L, Schwartz P J, Towbin J A, Vincent G M, Lehmann M H
Department of Medicine, University of Rochester (NY) School of Medicine and Dentistry 14642, USA.
Circulation. 1995 Nov 15;92(10):2929-34. doi: 10.1161/01.cir.92.10.2929.
The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome.
Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QTonset-c, QTpeak-c, QTc, and Tduration-c, in milliseconds) and the absolute height of the T wave (Tamplitude, in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n = 47), 7 (n = 30), and 11 (n = 76). Genotypic data were used to define each family member as being affected or unaffected with long QT syndrome. Affected members of all six families had longer QT intervals (QTonset-c, QTpeak-c, or QTc) than unaffected family members (P < .01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QTonset-c was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QTonset-c [mean +/- SD]: chromosome 3, 341 +/- 42 ms; chromosome 7, 290 +/- 56 ms; chromosome 11, 243 +/- 73 ms; P < .001); Tamplitude was generally quite small in the chromosome 7 genotype (lead II Tamplitude, mV: chromosome 3, 0.36 +/- 0.14; chromosome 7, 0.13 +/- 0.07; chromosome 11, 0.37 +/- 0.17; P < .001); and Tduration was particularly long in the chromosome 11 genotype (lead II Tduration-c: chromosome 3, 187 +/- 33 ms; chromosome 7, 191 +/- 51 ms; chromosome 11, 262 +/- 65 ms; P < .001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes.
Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.
长QT综合征是一种遗传性疾病，其特征为心室复极延长，易发生室性快速心律失常和心律失常性猝死。最近的连锁研究已证实该疾病在3号、7号和11号染色体上有三个不同的基因位点，并且在其中两条染色体上已鉴定出长QT综合征的特定突变基因。我们研究了与长QT综合征三种遗传上不同形式相关的家族成员的心电图T波形态（表型）。
对六个长QT综合征家族的153名成员测量了五个定量心电图复极参数，即四个经Bazett校正的时间间期（QT起始点校正值、QT峰值校正值、QTc和T波持续时间校正值，单位为毫秒）以及T波的绝对高度（T波振幅，单位为毫伏），这些家族与3号染色体（n = 47）、7号染色体（n = 30）和11号染色体（n = 76）上的标记相关。基因型数据用于将每个家族成员定义为患有或未患有长QT综合征。所有六个家族的患病成员的QT间期（QT起始点校正值、QT峰值校正值或QTc）均比未患病家族成员长（P <.01）。三种长QT综合征基因型中的每一种都与一些独特的心电图复极特征相关。在患病个体中，涉及3号染色体上心脏钠通道基因SCN5A突变的个体的QT起始点校正值异常延长（II导联QT起始点校正值[均值±标准差]：3号染色体，341±42毫秒；7号染色体，290±56毫秒；11号染色体，243±73毫秒；P <.001）；7号染色体基因型的T波振幅通常相当小（II导联T波振幅，毫伏：3号染色体，0.36±0.14；7号染色体，0.13±0.07；11号染色体，0.37±0.17；P <.001）；11号染色体基因型的T波持续时间特别长（II导联T波持续时间校正值：3号染色体，187±33毫秒；7号染色体，191±51毫秒；11号染色体，262±65毫秒；P <.001）。在aVF和V5导联中观察到类似的心电图表现。与每种基因型相关的定量复极参数存在相当大的变异性，三种基因型的T波形态存在重叠。
长QT综合征的三个不同基因位点，包括两个心脏离子通道基因的突变，与心电图上不同的表型T波形态相关。本研究为遗传因素对心室复极心电图表现的影响提供了见解。
