Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene

被引：32

作者：

Shimizu, Hiroshi ^{[1
]}

Toyoshima, Yasuko ^{[1
]}

Shiga, Atsushi ^{[1
]}

Yokoseki, Akio ^{[2
]}

Arakawa, Keiko ^{[2
]}

Sekine, Yumi ^{[2
]}

Shimohata, Takayoshi ^{[2
]}

Ikeuchi, Takeshi ^{[2
]}

Nishizawa, Masatoyo ^{[2
]}

Kakita, Akiyoshi ^{[1
]}

Onodera, Osamu ^{[3
]}

Takahashi, Hitoshi ^{[1
]}

机构：

[1] Niigata Univ, Brain Res Inst, Dept Pathol, Chuo Ku, Niigata 9518585, Japan

[2] Niigata Univ, Brain Res Inst, Dept Neurol, Niigata 951, Japan

[3] Niigata Univ, Brain Res Inst, Dept Mol Neurosci, Niigata, Japan

来源：

ACTA NEUROPATHOLOGICA | 2013年 / 126卷 / 03期

关键词：

Amyotrophic lateral sclerosis; SQSTM1; gene; Compound heterozygote; Neuropathology; p62; TDP-43; AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; HEXANUCLEOTIDE REPEAT EXPANSION; SUPEROXIDE-DISMUTASE; TDP-43; INCLUSIONS; C9ORF72; DIAGNOSIS; BODIES; FTD;

D O I：

10.1007/s00401-013-1150-5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：453 / 459

页数：7

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