Scotter Emma L, Smyth Leon, Bailey J Ames W T, Wong Chun-Hao, de Majo Martina, Vance Caroline A, Synek Beth J, Turner Clinton, Pereira Jennifer, Charleston Alison, Waldvogel Henry J, Curtis Maurice A, Dragunow Mike, Shaw Christopher E, Smith Bradley N, Faull Richard L M
Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Pharmacology, University of Auckland, Auckland, New Zealand.
Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Pharmacology, University of Auckland, Auckland, New Zealand.
Neurobiol Aging. 2017 Jan;49:214.e1-214.e5. doi: 10.1016/j.neurobiolaging.2016.06.019. Epub 2016 Jul 5.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, which causes progressive and eventually fatal loss of motor function. Here, we describe genetic and pathologic characterization of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, University of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats (DPRs), and ubiquilin. We identified 2 cases with C9ORF72 repeat expansions. Both harbored phosphorylated TDP-43 and DPR inclusions. We show that DPR inclusions can incorporate or occur independently of ubiquilin. We also identified 1 case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This is the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.
肌萎缩侧索硬化症（ALS）是一种毁灭性的神经退行性疾病，会导致运动功能逐渐丧失并最终致命。在此，我们描述了在近20年里从新西兰奥克兰大学解剖学系和脑研究中心存储的19例ALS患者脑组织中进行的基因和病理学特征分析。我们筛查了超氧化物歧化酶1（SOD1）、转录激活反应DNA结合蛋白43（TARDBP）、融合蛋白（FUS）和第9号染色体开放阅读框72（C9ORF72）基因的突变，以及由磷酸化TDP-43、二肽重复序列（DPRs）和泛素连接酶引起的神经病理学变化。我们鉴定出2例C9ORF72重复序列扩增病例。这两例均含有磷酸化TDP-43和DPR包涵体。我们发现DPR包涵体可以包含泛素连接酶或独立于泛素连接酶出现。我们还鉴定出1例泛素连接酶2（UBQLN2）基因突变病例，该病例显示有磷酸化TDP-43和特征性泛素连接酶蛋白包涵体。这是新西兰首例关于ALS遗传学的研究，使新西兰加入到在ALS病例中检测到C9ORF72重复序列扩增和UBQLN2基因突变的国家行列，且这一行列中的国家数量不断增加。
