晚期庞贝病患者酸性α-葡萄糖苷酶活性低的分子分析和蛋白加工。
Molecular analysis and protein processing in late-onset Pompe disease patients with low levels of acid α-glucosidase activity.
机构信息
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA.
出版信息
Muscle Nerve. 2011 May;43(5):665-70. doi: 10.1002/mus.21933.
INTRODUCTION
Pompe disease (glycogen storage disease type II, acid maltase deficiency) is caused by deficiency of lysosomal acid α-glucosidase (GAA). A few late-onset patients have been reported with skin fibroblast GAA activity levels of <2%.
METHODS
We measured GAA activity in skin fibroblasts from 101 patients with late-onset Pompe disease. Whenever possible, we performed Western blot analysis and correlated the results with GAA activity and GAA gene mutations.
RESULTS
Thirteen patients (13%) had skin fibroblast GAA activity of <1% of normal. Although there was wide genetic heterogeneity, none of these patients carried the common late-onset mutation c.-32-13T > G. We performed Western blot on 11 patients with <1% GAA activity. All produced GAA protein that was at lower levels and/or was abnormally processed.
DISCUSSION
There is no common mutation associated with <1% GAA activity in late-onset Pompe disease patients. Most patients produce unprocessed forms of GAA protein compared with patients with higher GAA activity.
简介
庞贝病（糖原贮积病 II 型，酸性麦芽糖酶缺乏症）是由溶酶体酸性α-葡萄糖苷酶（GAA）缺乏引起的。已有少数迟发性患者的皮肤成纤维细胞 GAA 活性<2%。
方法
我们测量了 101 例迟发性庞贝病患者皮肤成纤维细胞中的 GAA 活性。只要有可能，我们就进行 Western blot 分析，并将结果与 GAA 活性和 GAA 基因突变相关联。
结果
13 名患者（13%）的皮肤成纤维细胞 GAA 活性<正常的 1%。尽管存在广泛的遗传异质性，但这些患者均未携带常见的迟发性突变 c.-32-13T > G。我们对 11 名 GAA 活性<1%的患者进行了 Western blot 分析。所有患者产生的 GAA 蛋白水平较低，/或处理异常。
讨论
在迟发性庞贝病患者中，与<1% GAA 活性相关的没有常见突变。与 GAA 活性较高的患者相比，大多数患者产生未加工的 GAA 蛋白。
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