Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations
Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations
复制标题
DOI：
10.1172/jci200316336
复制
发表时间：
2003-01-01
影响因子：
15.9
通讯作者：
McKenna, WJ
中科院分区：
文献类型：
--
作者：
Mogensen, J;Kubo, T;McKenna, WJ
限制性心肌病（RCM）是一种罕见的心肌疾病，其特征是在正常或接近正常的室壁厚度和收缩功能的情况下，心室充盈受损，体积减少。这种疾病可能与全身性疾病有关，但最常见的是特发性疾病。我们发现一个大家族，其中个体受特发性RCM或肥厚型心肌病（HCM）影响。对选定的肌节收缩蛋白基因的连锁分析确定心肌肌钙蛋白I（TNNI3）为可能的疾病基因。随后的突变分析发现了一个新的错义突变，该突变与该家系中的疾病共分离（lod评分：4.8）。为了确定特发性RCM是否是TNNI3突变临床表达的一部分，在另外9名具有限制性充盈模式、双心房扩张、正常收缩功能和正常壁厚的不相关RCM患者中进行了基因的遗传研究。在这9名RCM患者中的6名中鉴定出TNNI3突变。在年轻个体中发现的两种突变是新生突变。所有突变均出现在该基因的保守和功能重要的结构域。特发性RCM患者中TNNI3突变的鉴定表明该表型是遗传性肌节收缩蛋白疾病谱的一部分。
Restrictive cardiomyopathy (RCM) is an uncommon heart muscle disorder characterized by impaired filling of the ventricles with reduced volume in the presence of normal or near normal wall thickness and systolic function. The disease may be associated with systemic disease but is most often idiopathic. We recognized a large family in which individuals were affected by either idiopathic RCM or hypertrophic cardiomyopathy (HCM). Linkage analysis to selected sarcomeric contractile protein genes identified cardiac troponin I (TNNI3) as the likely disease gene. Subsequent mutation analysis revealed a novel missense mutation, which cosegregated with the disease in the family (lod score: 4.8). To determine if idiopathic RCM is part of the clinical expression of TNNI3 mutations, genetic investigations of the gene were performed in an additional nine unrelated RCM patients with restrictive filling patterns, bi-atrial dilatation, normal systolic function, and normal wall thickness. TNNI3 mutations were identified in six of these nine RCM patients. Two of the mutations identified in young individuals were de novo mutations. All mutations appeared in conserved and functionally important domains of the gene. The identification of TNNI3 mutations in idiopathic RCM patients indicates that this phenotype is part of the spectrum of hereditary sarcomeric contractile protein disease.