Division of Neuropathology, University of British Columbia , Vancouver , Canada.
Division of Neurology, University of British Columbia , Vancouver , Canada , and.
Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):568-575. doi: 10.1080/21678421.2019.1632347. Epub 2019 Jun 27.
Mutations in the TANK binding kinase 1 gene () are associated with amyotrophic lateral sclerosis and/or frontotemporal dementia; however, the range of clinical phenotypes and neuropathological changes associated with these mutations have not yet been completely elucidated. We present the detailed clinical, neuroimaging, and neuropathological features of two brothers carrying the p.Gly272_Thr331del mutation. Both presented with very similar and unusual clinical features including primary progressive aphasia and asymmetric-onset primary lateral sclerosis (PLS). Repeated electrophysiological studies failed to reveal any lower motor neuron involvement. Neuropathological evaluation of both cases revealed frontotemporal lobar degeneration with TDP-43 proteinopathy type B and selective involvement of upper motor neurons with TDP-43 inclusions. The stereotypical clinical presentation and neuropathological findings in these cases widen the phenotypic spectrum of mutations and provide insights into the pathogenesis of PLS.
TANK 结合激酶 1 基因 () 的突变与肌萎缩侧索硬化症和/或额颞叶痴呆有关；然而，这些突变相关的临床表型和神经病理学变化范围尚未完全阐明。我们介绍了携带 p.Gly272_Thr331del 突变的两兄弟的详细临床、神经影像学和神经病理学特征。两者均表现出非常相似且不寻常的临床特征，包括原发性进行性失语症和非对称起病的原发性侧索硬化症 (PLS)。重复的电生理研究未能发现任何下运动神经元受累。对两个病例的神经病理学评估显示额颞叶变性，伴有 TDP-43 蛋白病 B 型和上运动神经元的选择性受累，伴有 TDP-43 包涵体。这些病例的典型临床表现和神经病理学发现拓宽了 突变的表型谱，并为 PLS 的发病机制提供了深入了解。
