Abstract
The 2011 discovery of the pathogenic hexanucleotide repeat expansion (HRE) in C9orf72, the leading genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), marked a breakthrough in the effort to unravel the etiology of these conditions. Ten years later, clinicians are still working to integrate the implications of this discovery into the care of individuals with ALS and/or FTD. Consensus management guidelines for ALS do not comprehensively address the issue of genetic testing, and questions remain about whom to test, what counseling should be provided before and after testing, laboratory methods, and test interpretation. These challenges have contributed to inconsistent clinical practices and present barriers to patients wishing to access testing. This review summarizes the clinical impact of the discovery of the C9orf72 HRE, outlines ongoing challenges, and provides recommendations for C9orf72 testing, counseling, and research.
Glossary
- ALS=
- amyotrophic lateral sclerosis;
- FTD=
- frontotemporal dementia;
- HRE=
- hexanucleotide repeat expansion;
- RP-PCR=
- repeat-primed PCR
Footnotes
Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article.
The Article Processing charge was funded by the Ohio State University Wexner Medical Center.
- Received July 25, 2020.
- Accepted in final form October 19, 2020.
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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