Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease)
Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease)
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DOI：
10.1038/35022604
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发表时间：
2000-08-24
期刊：
影响因子：
64.8
通讯作者：
Hirano, M
中科院分区：
文献类型：
--
作者：
Nishino, I;Fu, J;Hirano, M
“溶酶体糖原贮积病伴正常酸性麦芽糖酶”，最初由Danon et al. (1)临床上以心肌病、肌病和变异性智力低下为特征。该疾病的病理标志是骨骼肌和心肌细胞中含有自噬物质和糖原的胞浆内空泡。肌膜蛋白和基膜与空泡膜相关（2，3）。在此，我们报告了10例不相关的患者，包括最初病例报告（1）中的1例患者，他们患有主要溶酶体膜蛋白LAMP-2的原发性缺陷。根据这些结果以及LAMP-2缺陷小鼠表现出类似的空泡性心脏骨骼肌病的发现，我们得出结论，原发性LAMP-2缺陷是Danon病的原因（4）。据我们所知，这是第一例由溶酶体结构蛋白而不是酶蛋白突变引起的人类心肌病。
"Lysosomal glycogen storage disease with normal acid maltase'', which was originally described by Danon et al.(1), is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes(2,3). Here we report ten unrelated patients, including one of the patients from the original case report(1), who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease(4). To our knowledge this is the first example of human cardiopathymyopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.