Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions.
Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions.
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DOI：
10.1111/j.1750-3639.2010.00413.x
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Lomen-Hoerth C
中科院分区：
文献类型：
--
作者：
Huang EJ;Zhang J;Geser F;Trojanowski JQ;Strober JB;Dickson DW;Brown RH Jr;Shapiro BE;Lomen-Hoerth C
幼年型肌萎缩侧索硬化症（ALS）伴嗜碱性包涵体是一种公认的疾病。然而，对这种毁灭性疾病的分子基础知之甚少。在这里，我们提出了两个年轻女性的遗传和神经病理学特征与致命的快速进展ALS嗜碱性夹杂物。在一个病例中，在FUS/TLS（肉瘤融合/脂肪肉瘤易位）基因中检测到种系突变（P525 L），而在另一个病例中未发现突变。在这两种情况下，尸检发现严重损失的脊髓运动神经元与剩余的神经元显示嗜碱性包涵体，含有异常聚集的FUS蛋白和无序的细胞内细胞器，包括线粒体和内质网。在这两名患者中，FUS阳性包涵体也检测到大脑皮质的IV-V层和脑干的几个核团的神经元。与此相反，迟发性散发性ALS患者的脊髓运动神经元没有表现出FUS蛋白异常积累的证据。这些结果强调了FUS突变和病理在快速进展的青少年ALS中的重要性。此外，我们的研究代表了FUS/TLS基因突变的快速进展的青少年ALS患者的神经病理学发现的第一个详细特征。
Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a well-recognized entity. However, the molecular underpinnings of this devastating disease are poorly understood. Here, we present genetic and neuropathological characterizations in two young women with fatal rapidly progressive ALS with basophilic inclusions. In one case, a germline mutation (P525L) was detected in the FUS/TLS (fused in sarcoma/translocated in liposarcoma) gene, whereas no mutation was identified in the other case. Postmortem examination in both cases revealed severe loss of spinal motor neurons with remaining neurons showing basophilic inclusions that contain abnormal aggregates of FUS proteins and disorganized intracellular organelles, including mitochondria and endoplasmic reticulum. In both patients, the FUS-positive inclusions were also detected in neurons in layers IV–V of cerebral cortex and several brainstem nuclei. In contrast, spinal motor neurons in patients with late-onset sporadic ALS showed no evidence of abnormal accumulation of FUS protein. These results underscore the importance of FUS mutations and pathology in rapidly progressive juvenile ALS. Furthermore, our study represents the first detailed characterizations of neuropathological findings in rapidly progressive juvenile ALS patients with a mutation in the FUS/TLS gene.
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影响因子：
56.9
作者：
Kwiatkowski, T. J., Jr.;Bosco, D. A.;Brown, R. H., Jr.
通讯作者：
Brown, R. H., Jr.
影响因子：
12.7
作者：
Fujita, Y;Okamoto, K;Gonatas, NK
通讯作者：
Gonatas, NK
影响因子：
--
作者：
Geser, Felix;Martinez-Lage, Maria;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
--
作者：
Geser, Felix;Brandmeir, Nicholas J.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
4.4
作者：
Aizawa, H;Kimura, T;Kikuchi, K
通讯作者：
Kikuchi, K