Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene
Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene
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DOI：
10.1007/s00401-013-1150-5
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发表时间：
2013-09-01
影响因子：
12.7
通讯作者：
Takahashi, Hitoshi
中科院分区：
文献类型：
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作者：
Shimizu, Hiroshi;Toyoshima, Yasuko;Takahashi, Hitoshi
越来越多的证据表明，编码 p62 蛋白的 SQSTM1 基因的杂合突变与肌萎缩侧索硬化症 (ALS) 相关。在这里，我们报告了一位患有散发性迟发性 ALS 的日本患者，该患者携带复合杂合 SQSTM1 突变 (p.[Val90Met];[Val153Ile])。尸检显示，虽然 TDP-43 病理学相当普遍，但下运动神经元 (LMN) 中选择性出现 p62 阳性/TDP-43 阴性细胞质内含物是一个特征。没有发现布尼纳的尸体。从超微结构上看，在脊髓前角细胞中观察到的 p62 阳性细胞质内含物由核糖体样颗粒的聚集体和丝状结构的混合束组成。另一个有趣的特征是伴随的路易体病理学。该患者 LMN 中出现的独特 p62 病理表明 SQSTM1 突变在 ALS 亚型发展中的致病作用。
Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). Here, we report a Japanese patient with sporadic, late-onset ALS who harbored compound heterozygous SQSTM1 mutations (p.[Val90Met];[Val153Ile]). Autopsy examination revealed that although TDP-43 pathology was rather widespread, the selective occurrence of p62-positive/TDP-43-negative cytoplasmic inclusions in the lower motor neurons (LMNs) was a characteristic feature. No Bunina bodies were found. Ultrastructurally, p62-positive cytoplasmic inclusions observed in the spinal anterior horn cells were composed of aggregates of ribosome-like granules and intermingled bundles of filamentous structures. Another feature of interest was concomitant Lewy body pathology. The occurrence of distinct p62 pathology in the LMNs in this patient indicates the pathogenic role of SQSTM1 mutations in the development of a subset of ALS.