| Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation. | |
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MedLine Citation:
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PMID: 21604077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutations in the gene encoding the fused in sarcoma (FUS) protein are responsible for ~3% of familial amyotrophic lateral sclerosis (ALS) and <1% of sporadic ALS (ALS-FUS). Descriptions of the associated neuropathology are few and largely restricted to individual case reports. To better define the neuropathology associated with FUS mutations, we have undertaken a detailed comparative analysis of six cases of ALS-FUS that include sporadic and familial cases, with both juvenile and adult onset, and with four different FUS mutations. We found significant pathological heterogeneity among our cases, with two distinct patterns that correlated with the disease severity and the specific mutation. Frequent basophilic inclusions and round FUS-immunoreactive (FUS-ir) neuronal cytoplasmic inclusions (NCI) were a consistent feature of our early-onset cases, including two with the p.P525L mutation. In contrast, our late-onset cases that included two with the p.R521C mutation had tangle-like NCI and numerous FUS-ir glial cytoplasmic inclusions. Double-labeling experiments demonstrated that many of the glial inclusions were in oligodendrocytes. Comparison with the neuropathology of cases of frontotemporal lobar degeneration with FUS-ir pathology showed significant differences and suggests that FUS mutations are associated with a distinct pathobiology. |
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Authors:
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Ian R A Mackenzie; Olaf Ansorge; Michael Strong; Juan Bilbao; Lorne Zinman; Lee-Cyn Ang; Matt Baker; Heather Stewart; Andrew Eisen; Rosa Rademakers; Manuela Neumann |
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Publication Detail:
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Type: Case Reports; Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-05-21 |
Journal Detail:
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Title: Acta neuropathologica Volume: 122 ISSN: 1432-0533 ISO Abbreviation: Acta Neuropathol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-23 Completed Date: 2011-10-13 Revised Date: 2012-04-09 |
Medline Journal Info:
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Nlm Unique ID: 0412041 Medline TA: Acta Neuropathol Country: Germany |
Other Details:
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Languages: eng Pagination: 87-98 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of British Columbia and Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada. ian.mackenzie@vch.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Amyotrophic Lateral Sclerosis / genetics*, pathology* Female Humans Inclusion Bodies / pathology Male Medulla Oblongata / metabolism, pathology Middle Aged Motor Cortex / metabolism, pathology Motor Neurons / metabolism, pathology Mutation / genetics* Neuroglia / metabolism, pathology RNA-Binding Protein FUS / genetics*, metabolism Severity of Illness Index* Spinal Cord / metabolism, pathology Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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74580//Canadian Institutes of Health Research; R01 AG026251-02/AG/NIA NIH HHS; R01 AG26251/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA-Binding Protein FUS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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