Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene.
Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) account for 4 - 5% of familial cases of amyotrophic lateral sclerosis (ALS). We describe the identification and in vitro cellular characterization of a genetic mutation in a family in which the index case, and subsequently...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Informa Healthcare
2014
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| _version_ | 1826290768452517888 |
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| author | Kent, L Vizard, T Smith, B Topp, S Vance, C Gkazi, A Miller, J Shaw, C Talbot, K |
| author_facet | Kent, L Vizard, T Smith, B Topp, S Vance, C Gkazi, A Miller, J Shaw, C Talbot, K |
| author_sort | Kent, L |
| collection | OXFORD |
| description | Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) account for 4 - 5% of familial cases of amyotrophic lateral sclerosis (ALS). We describe the identification and in vitro cellular characterization of a genetic mutation in a family in which the index case, and subsequently her two children, each developed rapidly progressive ALS at a young age and died within a year of onset. Exome capture and sequencing revealed a mutation in the FUS gene consisting of a 2-bp deletion, c.1509_1510delAG, resulting in a predicted truncated protein, p.G504Wfs * 12, lacking the nuclear localization signal. Expression of this mutation in HEK293 and NSC-34 cells demonstrated severe cytoplasmic mislocalization of mutant FUS, and colocalization with stress granules when compared to wild-type, R521C and P525L mutant FUS. This study provides further evidence of a broad correlation between clinical severity of FUS-related ALS and mislocalization of the protein to the cytoplasm. |
| first_indexed | 2024-03-07T02:49:15Z |
| format | Journal article |
| id | oxford-uuid:ad183ff2-684f-48e2-a966-2e1557de5c36 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:49:15Z |
| publishDate | 2014 |
| publisher | Informa Healthcare |
| record_format | dspace |
| spelling | oxford-uuid:ad183ff2-684f-48e2-a966-2e1557de5c362022-03-27T03:33:14ZAutosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ad183ff2-684f-48e2-a966-2e1557de5c36EnglishSymplectic Elements at OxfordInforma Healthcare2014Kent, LVizard, TSmith, BTopp, SVance, CGkazi, AMiller, JShaw, CTalbot, KMutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) account for 4 - 5% of familial cases of amyotrophic lateral sclerosis (ALS). We describe the identification and in vitro cellular characterization of a genetic mutation in a family in which the index case, and subsequently her two children, each developed rapidly progressive ALS at a young age and died within a year of onset. Exome capture and sequencing revealed a mutation in the FUS gene consisting of a 2-bp deletion, c.1509_1510delAG, resulting in a predicted truncated protein, p.G504Wfs * 12, lacking the nuclear localization signal. Expression of this mutation in HEK293 and NSC-34 cells demonstrated severe cytoplasmic mislocalization of mutant FUS, and colocalization with stress granules when compared to wild-type, R521C and P525L mutant FUS. This study provides further evidence of a broad correlation between clinical severity of FUS-related ALS and mislocalization of the protein to the cytoplasm. |
| spellingShingle | Kent, L Vizard, T Smith, B Topp, S Vance, C Gkazi, A Miller, J Shaw, C Talbot, K Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. |
| title | Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. |
| title_full | Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. |
| title_fullStr | Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. |
| title_full_unstemmed | Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. |
| title_short | Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. |
| title_sort | autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma fus gene |
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