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Reference: Smith, BN, Topp, SD, Fallini, C et al., (2017). Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis. Science Translational Medicine, 9 (388), Article: eaad9157.Citable link to this page:

 

Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11–positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Accepted ManuscriptDate of acceptance:2016-10-13 Funder: Middlemass family   Funder: Heaton-Ellis Trust   Funder: Motor Neurone Disease Association   Funder: Medical Research Council   Funder: Psychiatry Research Trust of the Institute of Psychiatry   Funder: Guy’s and St Thomas’ Charity   Funder: Wellcome Trust   Funder: Noreen Murray Foundation   Funder: Medical Research Foudation   Funder: National Institute for Health Research   Funder: Maudsley NHS Foundation Trust   Funder: King’s College London   Funder: ALS Association   Funder: Japan Society for the Promotion of Science   Funder: Massachusetts Institute of Technology   Funder: Italian Ministry of Health   Funder: National Institutes of Health   Funder: American ALS Association   Funder: Project MinE   Funder: Instituto de Salud Carlos III   Funder: FUNDELA   Funder: Seventh Framework Programme   Funder: MND Association   Notes:Copyright © 2017 The Authors,some rights reserved;exclusive licenseeAmerican Associationfor the Advancementof Science. This is the accepted manuscript version of the article. The final version is available online from American Association for the Advancement of Science at: https://doi.org/10.1126/scitranslmed.aad9157

Bibliographic Details

Publisher: American Association for the Advancement of Science

Publisher Website: http://www.aaas.org/

Journal: Science Translational Medicinesee more from them

Publication Website: http://www.sciencetranslationalmedicine.org/

Volume: 9

Issue: 388

Extent: Article: eaad9157

Issue Date: 2017-05-03

pages:Article: eaad9157Identifiers

Uuid: uuid:bec636a4-2785-4873-b3e0-590c33d9225f

Urn: uri:bec636a4-2785-4873-b3e0-590c33d9225f

Pubs-id: pubs:652419

Doi: https://doi.org/10.1126/scitranslmed.aad9157

Issn: 1946-6234

Eissn: 1946-6242 Item Description

Type: journal-article;

Version: Accepted Manuscript

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Autor: Smith, BN - - - Topp, SD - - - Fallini, C - - - Shibata, H - - - Chen, H-J - - - Troakes, C - - - King, A - - - Ticozzi, N - - -

Fuente: https://ora.ox.ac.uk/objects/uuid:bec636a4-2785-4873-b3e0-590c33d9225f



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