Home › Research › Lewy body dementia
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS
DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA et al.. Neuron, 2011-09-21
Topic: Brain proteins, microglia and lab models
Several families have been reported with autosomal-dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to chromosome 9p21. Here, we report an expansion of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p. This same repeat expansion was identified in the majority of our families with a combined FTD/ALS phenotype and TDP-43-based pathology. Analysis of extended clinical series found the C9ORF72 repeat expansion to be the most common genetic abnormality in both familial FTD (11.7%) and familial ALS (23.5%). The repeat expansion leads to the loss of one alternatively spliced C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.
Key findings
- Here, we report an expansion of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p.
- Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.
Why it matters
In families with inherited frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) linked to chromosome 9p21, this study found an expanded GGGGCC repeat in the C9ORF72 gene. In the authors' clinical series it was the most common genetic abnormality: 11.7% of familial FTD and 23.5% of familial ALS. The authors call it "a major cause of both FTD and ALS", though the study concerns those diseases rather than Alzheimer's and tests no treatment or prevention.
Study details
- Effect size11.7%; 23.5%
- Evidence strengthLow
How this study scored 62/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 4,956 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 291.5 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 6 / 6 | Cited 189.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 127 other studies in this library |
| Still being cited | 4 / 4 | Cited 732 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Rosa Rademakers: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21944778) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., et al. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. https://doi.org/10.1016/j.neuron.2011.09.011
Vancouver
DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011. doi:10.1016/j.neuron.2011.09.011. PMID: 21944778.
BibTeX
@article{dejesushernandez2011-21944778,
author = {DeJesus-Hernandez, M. and Mackenzie, I. R. and Boeve, B. F. and Boxer, A. L. and Baker, M. and Rutherford, N. J. and Nicholson, A. M. and Finch, N. A. and others},
title = {{Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS}},
journal = {Neuron},
year = {2011},
doi = {10.1016/j.neuron.2011.09.011},
pmid = {21944778},
url = {https://doi.org/10.1016/j.neuron.2011.09.011}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 15.
Later studies that cite this one
127 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.