Familial amyotrophic lateral sclerosis with bulbar onset and a novel Asp101Tyr Cu/Zn superoxide dismutase gene mutation
Familial amyotrophic lateral sclerosis with bulbar onset and a novel Asp101Tyr Cu/Zn superoxide dismutase gene mutation
复制标题
DOI：
10.1007/s00401-004-0893-4
复制
发表时间：
2004-10-01
影响因子：
12.7
通讯作者：
Takahashi, H
中科院分区：
文献类型：
--
作者：
Tan, CF;Piao, YS;Takahashi, H
我们描述了一位患有家族性肌萎缩性侧索硬化症（FALS）的患者，我们在他的Cu/Zn超氧化物歧化酶（SOD1）基因的外显子4 （Asp101Tyr）上发现了一个新的错义突变。疾病开始时表现为球症状（快速进行性声音嘶哑），尸检显示退行性改变局限于上下运动神经元系统（更严格地说，运动优势较低，表现为模棱两可核最严重的退行性改变）。下运动神经元偶见胞浆内路易体样透明包涵体，对泛素和SOD1免疫反应，但对神经丝蛋白免疫阴性。这是第一例以声音嘶哑作为FALS最初表现的报道。这种SOD1基因突变可能与特定的临床病理表型有关。
We describe a patient with familial amyotrophic lateral sclerosis (FALS) in whom we identified a novel missense mutation in exon 4 (Asp101Tyr) of the Cu/Zn superoxide dismutase (SOD1) gene. The disease started with a bulbar symptom (rapidly progressive hoarseness) and at autopsy showed degenerative changes restricted to the upper and lower motor neuron systems (more strictly, with lower motor predominance, showing the most severe degeneration in the nucleus ambiguus). Occasional intracytoplasmic Lewy-body-like hyaline inclusions that were immunoreactive for ubiquitin and SOD1, but immunonegative for neurofilament protein, were found in the lower motor neurons. This is the first report of hoarseness as the initial manifestation of FALS. This SOD1 gene mutation may be associated with a particular clinicopathological phenotype.