Franklin, J.P., Cooper-Knock, J., Baheerathan, A. et al. (6 more authors) (2020) Concurrent sodium channelopathies and amyotrophic lateral sclerosis supports shared pathogenesis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 21 (7-8). pp. 627-630. ISSN 2167-8421
Abstract
Amyotrophic lateral sclerosis (ALS) is an invariably fatal adult-onset neurodegenerative disorder; approximately 10% of ALS is monogenic but all ALS exhibits significant heritability. The skeletal muscle sodium channelopathies are a group of inherited, non-dystrophic ion channel disorders caused by heterozygous point mutations in the SCN4A gene, leading to clinical manifestations of congenital myotonia, paramyotonia, and periodic paralysis syndromes. We provide clinical and genetic evidence of concurrence of these two rare disorders which implies a possible shared underlying pathophysiology in two patients. We then identify an enrichment of ALS-associated mutations in another sodium channel, SCN7A, from whole genome sequencing data of 4495 ALS patients and 1925 controls passing multiple testing correction (67 variants, p = 0.0002, Firth logistic regression). These findings suggest dysfunctional sodium channels may play a role upstream in the pathogenesis of ALS in a subset of patients, potentially opening the door to novel personalized medicine approaches.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Genetics; excitotoxicity; risk |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 Jul 2020 14:58 |
Last Modified: | 21 Jan 2022 10:16 |
Status: | Published |
Publisher: | Taylor & Francis |
Refereed: | Yes |
Identification Number: | 10.1080/21678421.2020.1786128 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:163649 |