Novel mutations support a role for Profilin 1 in the pathogenesis of ALS
Smith BN, Vance C, Scotter EL, Troakes C, Wong CH, Topp S, Maekawa S, King A et al.. Neurobiology of aging, 2014-10-31
Topic: Brain proteins, microglia and lab models
Mutations in the gene encoding profilin 1 (PFN1) have recently been shown to cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We sequenced the PFN1 gene in a cohort of ALS patients (n = 485) and detected 2 novel variants (A20T and Q139L), as well as 4 cases with the previously identified E117G rare variant (∼ 1.2%). A case-control meta-analysis of all published E117G ALS+/- frontotemporal dementia cases including those identified in this report was significant p = 0.001, odds ratio = 3.26 (95% confidence interval, 1.6-6.7), demonstrating this variant to be a susceptibility allele. Postmortem tissue from available patients displayed classic TAR DNA-binding protein 43 pathology. In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology. Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease.
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APA 7th
Smith, B. N., Vance, C., Scotter, E. L., Troakes, C., Wong, C. H., Topp, S., et al. (2015). Novel mutations support a role for Profilin 1 in the pathogenesis of ALS. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2014.10.032
Vancouver
Smith BN, Vance C, Scotter EL, Troakes C, Wong CH, Topp S, et al. Novel mutations support a role for Profilin 1 in the pathogenesis of ALS. Neurobiology of aging. 2015. doi:10.1016/j.neurobiolaging.2014.10.032. PMID: 25499087.
BibTeX
@article{smith2015-25499087,
author = {Smith, B. N. and Vance, C. and Scotter, E. L. and Troakes, C. and Wong, C. H. and Topp, S. and Maekawa, S. and King, A. and others},
title = {{Novel mutations support a role for Profilin 1 in the pathogenesis of ALS}},
journal = {Neurobiology of aging},
year = {2015},
doi = {10.1016/j.neurobiolaging.2014.10.032},
pmid = {25499087},
url = {https://doi.org/10.1016/j.neurobiolaging.2014.10.032}
}
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Key findings
- A case-control meta-analysis of all published E117G ALS+/- frontotemporal dementia cases including those identified in this report was significant p = 0.001, odds ratio = 3.26 (95% confidence interval, 1.6-6.7), demonstrating this variant to be a susceptibility allele.
- In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology.
- Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease.
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Study details
- Study designmeta-analysis
- Participants485
- Effect size1.2%
- Evidence strengthHigh
How this study scored 79/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 46 of the 58 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 485 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25499087) |
| Free to read | 2 / 2 | Free to read |
| Points | 46 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 46 of the 58 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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