Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN-42 C>G mutation
Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN-42 C>G mutation
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DOI：
10.1016/j.ejheart.2006.04.007
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发表时间：
2007-01-01
影响因子：
18.2
通讯作者：
Castro-Beiras, Alfonso
中科院分区：
文献类型：
--
作者：
Medin, Mania;Hermida-Prieto, Manuel;Castro-Beiras, Alfonso
背景资料：Phospholarnban是一种内源性肌浆网钙ATP酶抑制剂，对心脏收缩/舒张偶联具有调节作用。受磷蛋白基因（PLN）的突变与原发性心肌病（primary cardiomyopathies.Aims）相关，目的：筛选原发性心肌病患者群体中的PLN突变，并对突变进行功能分析。方法：我们对186例肥厚型或扩张型心肌病患者的PLN基因进行了SSCP突变筛查和DNA测序。为了研究启动子强度，我们构建了含荧光素酶基因的报告质粒，并在C6和C2Cl 2细胞系中进行了瞬时转染分析。结果：在1例晚发性家族性心尖肥厚性心肌病患者中发现PLN-42 C > G突变。在C6和C2 C12细胞系中，该突变分别使受磷蛋白启动子活性降低43%和47%。结论：PLN-42 C > G突变与该家系良性心尖肥厚型心肌病相关，但该家系中存在一名健康成人携带者，提示可能与其他遗传和环境因素有关。在我们的人群中，PLN基因突变并不是心肌病的常见原因。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Background: Phospholarnban is an endogenous sarcoplasmic reticulum calcium ATPase inhibitor with a regulatory effect on cardiac contraction/relaxation coupling. Mutations in the phospholamban gene (PLN) have been associated with primary cardiomyopathies.Aims: To screen for PLN mutations in our population of patients with primary cardiomyopathies and to perform functional analysis of the mutations identified.Methods: We performed SSCP mutational screening and DNA sequencing of the PLN gene in 186 patients with either hypertrophic or dilated cardiomyopathy. To study promoter strength we constructed reporter plasmids containing the luciferase gene and performed transient transfection analysis in C6 and C2Cl2 cell lines.Results: The PLN -42 C > G mutation was found in one patient with late onset familial apical hypertrophic cardiornyopathy. This mutation decreased phospholamban promoter activity by 43% and 47%, in C6 and C2C12 cell lines respectively. One son had mild apical hypertrophic cardiornyopathy and carried the mutation, another son with normal ECG and echocardiogram also had the mutation.Conclusion: The PLN -42 C > G mutation is associated with a benign form of apical hypertrophic cardiornyopathy in this family, though the presence of a healthy adult carrier suggests that other genetic and environmental factors could be involved. Other-wise, mutations in the PLN gene are not a frequent cause of cardiomyopathies in our population. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.