Shaw C E, Enayat Z E, Powell J F, Anderson V E, Radunovic A, al-Sarraj S, Leigh P N
Department of Clinical Neuroscience, Institute of Psychiatry, London, UK.
Neurology. 1997 Dec;49(6):1612-6. doi: 10.1212/wnl.49.6.1612.
We report the clinical, genetic, and neuropathologic findings in a patient with rapidly progressive familial amyotrophic lateral sclerosis (ALS). We detected a point mutation at codon 48 of the Cu/Zn superoxide dismutase gene (SOD1) leading to a substitution of histidine by glutamine in the copper-binding domain. The histopathologic features are consistent with those described in rapidly progressive sporadic ALS and do not support claims that sporadic and familial disease are different pathologic entities. Neurofilamentous accumulations, hyaline, and ubiquitinated inclusions were present in the motor cortex, brainstem, and anterior horn cells, but there was no evidence of abnormal SOD1 immunoreactivity. This confirms that the cytoskeletal pathology specific to ALS is secondary to an unknown biochemical disturbance caused by mutant SOD1 molecules and not its toxic accumulation.
我们报告了一名快速进展性家族性肌萎缩侧索硬化症（ALS）患者的临床、基因和神经病理学发现。我们在铜/锌超氧化物歧化酶基因（SOD1）的第48密码子处检测到一个点突变，该突变导致铜结合域中的组氨酸被谷氨酰胺取代。组织病理学特征与快速进展性散发性ALS中描述的特征一致，不支持散发性和家族性疾病是不同病理实体的说法。运动皮层、脑干和前角细胞中存在神经丝聚集、透明样物质和泛素化包涵体，但没有异常SOD1免疫反应性的证据。这证实了ALS特有的细胞骨架病理学是由突变SOD1分子引起的未知生化紊乱所致，而非其毒性积累。
