Mortalin mutations are not a frequent cause of early-onset Parkinson disease
Mortalin mutations are not a frequent cause of early-onset Parkinson disease
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DOI：
10.1016/j.neurobiolaging.2013.05.021
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发表时间：
2013-11-01
影响因子：
4.2
通讯作者：
Westenberger, Ana
中科院分区：
文献类型：
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作者：
Freimann, Karen;Zschiedrich, Katja;Westenberger, Ana
线粒体功能障碍和线粒体伴侣死亡蛋白（HSPA 9，GRP 75）参与了帕金森病（PD）的发病机制。我们筛选了139例早发性PD（EOPD）患者的mortalin突变，发现一个错义突变（p.L358P），而在279例对照个体中不存在。我们还在对照组中发现了一个额外的错义变体（p.T333K）。虽然这两个错义变化被预测为致病，我们检测到野生型和突变型死亡蛋白之间的亚细胞定位，线粒体形态，或呼吸功能没有差异。这些发现表明，死亡蛋白的变体（1）不是EOPD的主要原因;（2）发生在患者和对照组中;（3）不会导致线粒体功能受损。(C)2013 Elsevier Inc. All rights reserved.
Dysfunctional mitochondria and the mitochondrial chaperone mortalin (HSPA9, GRP75) have been implicated in the pathogenesis of Parkinson disease (PD). We screened 139 early-onset PD (EOPD) patients for mutations in mortalin revealing one missense change (p.L358P) that was absent in 279 control individuals. We also found one additional missense variant among the controls (p.T333K). Although both missense changes were predicted to be disease causing, we detected no differences in subcellular localization, mitochondrial morphology, or respiratory function between wild-type and mutant mortalin. These findings suggest that variants in mortalin (1) are not a major cause of EOPD; (2) occur in patients and controls; and (3) do not lead to functional impairment of mitochondria. (C) 2013 Elsevier Inc. All rights reserved.