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Title: | ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization |
Author: | Tazelaar, Gijs H. P. Boeynaems, Steven Decker, Mathias De Povedano, Mònica Assialioui, Abdelilah Project MinE ALS Sequencing Consortium |
Keywords: | Esclerosi lateral amiotròfica Genètica Amyotrophic lateral sclerosis Genetics |
Issue Date: | 1-Jan-2020 |
Publisher: | Oxford University Press (OUP) |
Abstract: | Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previously published data, the identification of an amyotrophic lateral sclerosis patient with a family history of spinocerebellar ataxia type 1, caused by polyglutamine expansions in ATXN1, suggested a similar disease association for the repeat expansion in ATXN1. We, therefore, performed a large-scale international study in 11 700 individuals, in which we showed a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis (P = 3.33 × 10-7). Subsequent functional experiments have shown that ATXN1 reduces the nucleocytoplasmic ratio of TDP-43 and enhances amyotrophic lateral sclerosis phenotypes in Drosophila, further emphasizing the role of polyglutamine repeat expansions in the pathophysiology of amyotrophic lateral sclerosis. |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/braincomms/fcaa064 |
It is part of: | Brain Communications, 2020, vol. 2, num.. 2 |
URI: | http://hdl.handle.net/2445/174313 |
Related resource: | https://doi.org/10.1093/braincomms/fcaa064 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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