Abstract
Objective: To determine whether GGGGCC (G4C2) repeat expansions at loci other than C9orf72 serve as common causes of amyotrophic lateral sclerosis (ALS).
Methods: We assessed G4C2 repeat number in 28 genes near known ALS and frontotemporal dementia (FTD) loci by repeat-primed PCR coupled with fluorescent fragment analysis in 199 patients with ALS (17 familial, 182 sporadic) and 136 healthy controls. We also obtained blood from patients with ALS4 for evaluation of repeats surrounding the SETX gene locus. C9orf72 expansions were evaluated in parallel.
Results: Expansions of G4C2 repeats in C9orf72 explained 8.8% of sporadic and 47% of familial ALS cases analyzed. Repeat variance was observed at one other locus, RGS14, but no large expansions were observed, and repeat sizes were not different between cases and controls. No G4C2 repeat expansions were identified at other ALS or FTD risk loci or in ALS4 cases.
Conclusions: G4C2 expansions near known ALS and FTD loci other than C9orf72 are not a common cause of ALS.
GLOSSARY
- ALS=
- amyotrophic lateral sclerosis;
- FTD=
- frontotemporal dementia;
- G4C2=
- GGGGCC;
- GWAS=
- genome-wide association studies;
- SNP=
- single-nucleotide polymorphism
Footnotes
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/ng for full disclosure forms. The Article Processing Charge was paid by the authors.
Supplemental data at Neurology.org/ng
- Received December 10, 2015.
- Accepted in final form March 1, 2016.
- © 2016 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.
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