Deficient RNA-editing enzyme ADAR2 in an amyotrophic lateral sclerosis patient with a FUSP525L mutation
Deficient RNA-editing enzyme ADAR2 in an amyotrophic lateral sclerosis patient with a FUSP525L mutation
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DOI：
10.1016/j.jocn.2015.12.039
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发表时间：
2016-10-01
影响因子：
2
通讯作者：
Kwak, Shin
中科院分区：
文献类型：
--
作者：
Aizawa, Hitoshi;Hideyama, Takuto;Kwak, Shin
肉瘤融合基因（FUS）的突变可导致肌萎缩侧索硬化（ALS），并且在伴有嗜碱性胞浆包涵体的散发性ALS患者中已报告了FUS基因突变。作用于RNA 2（ADAR 2）的腺苷脱氨酶（一种特异性催化GluA 2 Q/R位点编辑的酶）的缺乏已在大多数散发性ALS患者的相当大比例的脊髓运动神经元中报道。我们描述了GluA 2 Q/12位点编辑效率与FUSP 525 L患者中FUS阳性包涵体之间的关系。一名24岁的ALS女性患者出现嗜碱性细胞质包涵体，脊髓运动神经元中GluA 2 Q/R位点编辑效率显著降低，ADAR 2 mRNA水平显著降低。神经病理学检查显示，并不是所有的脊髓运动神经元表达ADAR 2，并显示在运动神经元中的细胞质包涵体呈FUS阳性，而与ADAR 2免疫反应无关。无磷酸化反式反应（TAR）DNA结合蛋白43 kDa（TDP-43）阳性包涵体，表明ADAR 2缺陷和TDP-43沉积之间没有紧密的相关性。ADAR 2缺陷可发生在具有FUSP 525 L突变的ALS患者中，并且与FUS阳性包涵体的存在无关。FUS相关的ALS可能与经典的散发性ALS具有神经退行性特征。(C)2016爱思唯尔有限公司版权所有。
Mutations in the fused in sarcoma (FUS) gene can cause amyotrophic lateral sclerosis (ALS), and FUS gene mutations have been reported in sporadic ALS patients with basophilic cytoplasmic inclusions. Deficiency of adenosine deaminase acting on RNA 2 (ADAR2), an enzyme that specifically catalyzes GluA2 Q/R site editing, has been reported in considerable proportions of spinal motor neurons of the majority of sporadic ALS patients. We describe the relationship between GluA2 Q/12 site-editing efficiency and FUS-positive inclusions in a patient with FUSP525L. A 24-year-old woman with ALS presented with basophilic cytoplasmic inclusions, significantly reduced GluA2 Q/R site-editing efficiency in the spinal motor neurons, and markedly decreased ADAR2 mRNA levels. Neuropathologic examination showed that not all spinal motor neurons expressed ADAR2 and revealed FUS-positive cytoplasmic inclusions in motor neurons irrespective of ADAR2 immunoreactivity. There were no phosphorylated transactive response (TAR) DNA-binding protein 43 kDa (TDP-43)-positive inclusions, indicating that there was no tight correlation between ADAR2 deficiency and TDP-43 deposition. ADAR2 deficiency can occur in ALS patients with a FUSP525L mutation and is unrelated to the presence of FUS-positive inclusions. FUS-associated ALS may share neurodegenerative characteristics with classical sporadic ALS. (C) 2016 Elsevier Ltd. All rights reserved.