Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy
Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy
复制标题
DOI：
10.1016/j.bbrc.2003.11.101
复制
发表时间：
2004-01-02
影响因子：
3.1
通讯作者：
Kimura, A
中科院分区：
文献类型：
--
作者：
Hayashi, T;Arimura, T;Kimura, A
肥厚型心肌病（HCM）和扩张型心肌病（DCM）分别由14和15种不同的疾病基因突变引起，在部分患者中，心肌病的疾病基因与肢带型肌营养不良症（LGMD）的疾病基因部分重叠。在这项研究中，我们研究了LGMD基因编码的小窝蛋白-3（CAV 3）的突变与HCM或DCM患者。在HCM的同胞病例中发现了Thr 63 Ser突变。由于突变被发现在参与LGMD引起的突变的残基，我们调查的功能变化，由于Thr 63 Ser突变相比，LGMD突变通过检查GFP标记的CAV 3蛋白的分布。观察到Thr 63 Ser突变降低了小窝蛋白-3的细胞表面表达，尽管与LGMD突变相比变化轻微。这些观察结果表明，HCM是CAV 3突变的临床谱。(C)2003年爱思唯尔公司All rights reserved.
Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are caused by mutations in 14 and 15 different disease genes, respectively, in a part of the patients and the disease genes for cardiomyopathy overlap in part with that for limb-girdle muscular dystrophy (LGMD). In this study, we examined an LGMD gene encoding caveolin-3 (CAV3) for mutation in the patients with HCM or DCM. A Thr63Ser mutation was identified in a sibling case of HCM. Because the mutation was found at the residue that is involved in the LGMD-causing mutations, we investigate the functional change due to the Thr63Ser mutation as compared with the LGMD mutations by examining the distribution of GFP-tagged CAV3 proteins. It was observed that the Thr63Ser mutation reduced the cell surface expression of caveolin-3, albeit the change was mild as compared with the LGMD mutations. These observations suggest that HCM is a clinical spectrum of CAV3 mutations. (C) 2003 Elsevier Inc. All rights reserved.