A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology
A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology
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DOI：
10.1016/j.neurobiolaging.2014.03.024
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发表时间：
2014-09-01
影响因子：
4.2
通讯作者：
Paetau, Anders
中科院分区：
文献类型：
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作者：
Pasanen, Petra;Myllykangas, Liisa;Paetau, Anders
我们描述了一个芬兰患者的临床，神经病理学和遗传特征与一种新的α-突触核蛋白（SNCA）突变A53 E。患者临床诊断为非典型帕金森病（PD），发病年龄为36岁。在60岁时进行的神经病理学分析中，在整个脑和脊髓中观察到高度丰富的SNCA病理学，显示多系统萎缩和PD的特征。神经元和神经胶质（包括少突胶质细胞）SNCA包涵体和神经突被发现在壳核，尾状核，杏仁核，颞叶和岛叶皮质，扣带回和海马CA 2 -3区特别突出。这些区域以及黑质和蓝斑显示神经元丢失和胶质增生。我们还发现TDP-43阳性，但大多数SNCA阴性的海马齿状筋膜核周包涵体。A53 E突变在另外2名患有帕金森综合征的亲属中发现。我们的研究结果表明，新的SNCA A53 E取代是一种致病突变，导致临床上帕金森综合征和病理上严重的多系统萎缩和PD型表型。(C)2014爱思唯尔公司All rights reserved.
We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel alpha-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy-and PD-type phenotype. (C) 2014 Elsevier Inc. All rights reserved.