A 5' dystrophin duplication mutation causes membrane deficiency of alpha-dystroglycan in a family with X-linked cardiomyopathy.
A 5' dystrophin duplication mutation causes membrane deficiency of alpha-dystroglycan in a family with X-linked cardiomyopathy.
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5 肌营养不良蛋白重复突变导致 X 连锁心肌病家族中 α-肌营养不良聚糖膜缺陷。
DOI：
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发表时间：
1997
影响因子：
5
通讯作者：
K. Campbell
中科院分区：
文献类型：
--
作者：
R. Bies;R. Bies;R. Bies;M. Maeda;M. Maeda;M. Maeda;S. Roberds;S. Roberds;S. Roberds;E. Holder;E. Holder;E. Holder;T. Bohlmeyer;T. Bohlmeyer;T. Bohlmeyer;James B. Young;James B. Young;James B. Young;K. Campbell;K. Campbell;K. Campbell
肌营养不良蛋白基因中的5 '-突变可导致心肌病而没有临床上明显的骨骼肌病变。抗肌萎缩蛋白突变对人心脏中抗肌萎缩蛋白相关蛋白（DAP）复合物的组装和稳定性的影响尚未完全了解。在一个有X连锁家系和严重扩张型心肌病的家族中，探讨了抗肌萎缩蛋白复合物的分子缺陷。抗肌营养不良蛋白基因分析表明，5'重复涉及外显子2-7，其编码抗肌营养不良蛋白的N-末端肌动蛋白结合结构域。核糖核酸酶保护和PCR分析表明，与骨骼肌相比，心脏中肌肉启动子转录的肌营养不良蛋白mRNA减少。免疫印迹法观察到心肌肌营养不良蛋白缺乏，免疫细胞化学法观察到心肌肌营养不良蛋白缺乏膜定位。肌营养不良蛋白相关蛋白utrophin的心脏表达增加，并且43 kDa（β-肌营养不良蛋白聚糖）、50 kDa（α-肌聚糖）和59 kDa（突触营养蛋白）肌营养不良蛋白相关蛋白（DAP）被共分离并以接近正常的量存在于膜中。然而，心肌肌营养不良蛋白缺乏和肌营养不良蛋白表达增加与细胞外156 kDa肌营养不良蛋白相关糖蛋白（α-肌营养不良蛋白聚糖）结合到心肌细胞膜的损失。α-肌营养不良聚糖负责肌营养不良蛋白复合物与细胞外基质蛋白层粘连蛋白的连接。因此，在X连锁心肌病（XLCM）中，5'肌营养不良蛋白突变可降低心脏肌营养不良蛋白mRNA、蛋白表达和肌营养不良蛋白功能。膜相关的β-肌营养不良蛋白聚糖、α-肌聚糖、突触营养蛋白和肌营养不良蛋白的存在不足以维持心脏功能。该XLCM家族具有5'肌营养不良蛋白基因突变，导致心脏肌营养不良蛋白缺乏和α-肌营养不良蛋白聚糖膜结合丧失。
5'-mutations in the dystrophin gene can result in cardiomyopathy without clinically-apparent skeletal myopathy. The effect of dystrophin mutations on the assembly and stability of the dystrophin associated protein (DAP) complex in human heart are not fully understood. The molecular defect in the dystrophin complex was explored in a family with an X-linked pedigree and severe dilated cardiomyopathy. Dystrophin gene analysis demonstrated a 5' duplication involving exons 2-7, which encodes the N-terminal actin binding domain of dystrophin. Ribonuclease protection and PCR assays demonstrated a reduction in muscle promoter transcribed dystrophin mRNA in the heart compared to skeletal muscle. A deficiency of cardiac dystrophin protein was observed by Western blot and lack of membrane localization by immunocytochemistry. The cardiac expression of the dystrophin related protein utrophin was increased, and the 43 kDa (beta-dystroglycan), 50 kDa (alpha-sarcoglycan) and 59 kDa (syntrophin) dystrophin associated proteins (DAPs) were co-isolated and present in nearly normal amounts in the membrane. However, cardiac dystrophin deficiency and increased utrophin expression were associated with loss of extracellular 156 kDa dystrophin associated glycoprotein (alpha-dystroglycan) binding to the cardiomyocyte membrane. alpha-Dystroglycan is responsible for linkage of the dystrophin complex to the extracellular matrix protein laminin. Therefore, 5' dystrophin mutations can reduce cardiac dystrophin mRNA, protein expression, and dystrophin function in X-linked cardiomyopathy (XLCM). The presence of membrane-associated beta-dystroglycan, alpha-sarcoglycan, syntrophin, and utrophin are insufficient to maintain cardiac function. This XLCM family has a 5' dystrophin gene mutation resulting in cardiac dystrophin deficiency and a loss of alpha-dystroglycan membrane binding.
影响因子：
11.2
作者：
Flanigan, Kevin M.;Ceco, Ermelinda;Lamar, Kay-Marie;Kaminoh, Yuuki;Dunn, Diane M.;Mendell, Jerry R.;King, Wendy M.;Pestronk, Alan;Florence, Julaine M.;Mathews, Katherine D.;Finkel, Richard S.;Swoboda, Kathryn J.;Gappmaier, Eduard;Howard, Michael T.;Day, John W.;McDonald, Craig;McNally, Elizabeth M.;Weiss, Robert B.
通讯作者：
Weiss, Robert B.
影响因子：
158.5
作者：
MICHELS, VV;MOLL, PP;TAZELAAR, HD
通讯作者：
TAZELAAR, HD