Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction
Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction
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DOI：
10.1016/j.jacc.2003.10.021
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发表时间：
2003-12-03
影响因子：
24
通讯作者：
Towbin, JA
中科院分区：
文献类型：
--
作者：
Vatta, M;Mohapatra, B;Towbin, JA
我们评估了Cypher/ZASP在扩张型心肌病（DCM）伴或不伴孤立性左心室心肌致密化不全（INLVM.Background）发病机制中的作用，扩张型心肌病的特征是左心室扩张和收缩功能障碍，伴有心力衰竭的体征，在30%至40%的病例中遗传。遗传异质性已被确定为多个细胞骨架和肌节基因突变引起的表型。此外，伴有肥厚性扩张左心室、心室功能障碍和深部小梁形成的INLVM也是遗传性的，迄今为止鉴定的基因与导致DCM的基因不同。Cypher/ZASP是一个新发现的基因编码的蛋白质是一个组成部分的Z线在骨骼肌和心肌muscle.Methods诊断DCM进行超声心动图，心电图，体格检查。此外，测量肌酸激酶的肌肉亚型的水平，以评估骨骼肌受累。采用变性高效液相色谱法（DHPLC）和直接测序法对Cypher/ZASP基因进行筛选。在患有家族性或散发性DCM或INLVM的患者中，在6名先证者（6%的病例）中发现了5种突变。体外研究表明，细胞骨架混乱的细胞转染突变的Cypher/ZASP.CONCLUSIONS这些数据表明，突变的Cypher/ZASP可以导致DCM和INLVM，并确定一个机制的基础。(C)2003年由美国心脏病学会基金会。
OBJECTIVES We evaluated the role of Cypher/ZASP in the pathogenesis of dilated cardiomyopathy (DCM) with or without isolated non-compaction of the left ventricular myocardium (INLVM).BACKGROUND Dilated cardiomyopathy, characterized by left ventricular dilation and systolic dysfunction with signs of heart failure, is genetically transmitted in 30% to 40% of cases. Genetic heterogeneity has been identified with mutations in multiple cytoskeletal and sarcomeric genes causing the phenotype. In addition, INLVM with a hypertrophic dilated left ventricle, ventricular dysfunction, and deep trabeculations, is also inherited, and the genes identified to date differ from those causing DCM. Cypher/ZASP is a newly identified gene encoding a protein that is a component of the Z-line in both skeletal and cardiac muscle.METHODS Diagnosis of DCM was performed by echocardiogram, electrocardiogram, and physical examination. In addition, levels of the muscular isoform of creatine kinase were measured to evaluate for skeletal muscle involvement. Cypher/ZASP was screened by denaturing high performance liquid chromatography (DHPLC) and direct deoxyribonucleic acid sequencing.RESULTS We identified and screened 100 probands with left ventricular dysfunction. Five mutations in six probands (6% of cases) were identified in patients with familial or sporadic DCM or INLVM. In vitro studies showed cytoskeleton disarray in cells transfected with mutated Cypher/ZASP.CONCLUSIONS These data suggest that mutated Cypher/ZASP can cause DCM and INLVM and identify a mechanistic basis. (C) 2003 by the American College of Cardiology Foundation.