Sudden death due to troponin T mutations
Sudden death due to troponin T mutations
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DOI：
10.1016/s0735-1097(96)00530-x
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发表时间：
1997-03-01
影响因子：
24
通讯作者：
Watkins, H
中科院分区：
文献类型：
--
作者：
Moolman, JC;Corfield, VA;Watkins, H
目标.本研究旨在验证心肌肌钙蛋白T基因突变引起的肥厚型心肌病的临床和预后特征的初步观察。年轻人心脏性猝死最常见的原因是肥厚性心肌病，通常是家族性的。导致家族性肥厚型心肌病的突变已在许多收缩蛋白基因中被鉴定，提高了对风险受试者进行遗传筛查的可能性。先前的报告表明，心肌肌钙蛋白T基因的突变是值得注意的，因为它们与特别差的预后有关，但仅与轻度肥厚有关。鉴于某些基因型与表型相关性的变异性，进一步分析心肌肌钙蛋白T突变已成为当务之急。使用核糖核酸酶保护试验对肥厚型心肌病受试者的脱氧核糖核酸进行心肌肌钙蛋白T突变筛查。聚合酶链反应为基础的检测一个新的突变基因型成员的两个受影响的家系。基因携带者通过超声心动图和心电图检查，并获得家族史。一种新的心肌肌钙蛋白T基因突变，精氨酸92色氨酸，在两个受影响的家系的48名成员中的19人被确定。临床表型的特点是最小肥大（平均[+/-SD]最大心室壁厚度11.3 +/- 5.4 mm）和临床标准的低疾病检出率（超声心动图为40%），但心源性猝死发生率高（平均年龄17 +/- 9岁）。这些数据支持了明显不同的心肌肌钙蛋白T基因突变产生一致的疾病表型的观察结果。因为这是一个预后不良，尽管看似轻微或无法检测到的肥大，在这个位点的基因分型可能是特别有益的患者管理和咨询。(C)1997年，美国心脏病学会。
Objectives. This study was designed to verify initial observations of the clinical and prognostic features of hypertrophic cardiomyopathy caused by cardiac troponin T gene mutations.Background. The most common cause of sudden cardiac death in the young is hypertrophic cardiomyopathy, which is usually familial. Mutations causing familial hypertrophic cardiomyopathy have been identified in a number of contractile protein genes, raising the possibility of genetic screening for subjects at risk A previous report suggested that mutations in the cardiac troponin T gene were notable because they were associated with a particularly poor prognosis but only mild hypertrophy. Given the variability of some genotype:phenotype correlations, further analysis of cardiac troponin T mutations has been a priority.Methods. Deoxyribonucleic acid from subjects with hypertrophic cardiomyopathy was screened for cardiac troponin T mutations using a ribonuclease protection assay. Polymerase chain reaction-based detection of a novel mutation was used to genotype members of two affected pedigrees. Gene carriers were examined by echocardiography and electrocardiology, and a family history was obtained.Results. A novel cardiac troponin T gene mutation, arginine 92 tryptophan, was identified in 19 of 48 members of two affected pedigrees. The clinical phenotype was characterized by minimal hypertrophy (mean [+/-SD] maximal ventricular wall thickness 11.3 +/- 5.4 mm) and low disease penetrance by clinical criteria (40% by echocardiography) but a high incidence of sudden cardiac death (mean age 17 +/- 9 years).Conclusions. These data support the observation that apparently diverse cardiac troponin T gene mutations produce a consistent disease phenotype. Because this is one of poor prognosis, despite deceptively mild or undetectable hypertrophy, genotyping at this locus may be particularly informative in patient management and counseling. (C) 1997 by the American College of Cardiology.