Novel p.Ile151Val mutation in VCP in a patient of African American descent with sporadic ALS
Bibliographic record
Abstract
The valosin containing protein (VCP) is a member of the AAA-ATPase family, a group of enzymatic molecular chaperones that have been associated with a range of cellular processes including ubiquitin-proteasome mediated degradation, membrane fusion, apoptosis, cell-cycle control, and autophagy.1 Mutations in VCP were first identified to cause familial inclusion body myopathy with early-onset Paget disease and frontotemporal dementia2 (IBMPFD) and more recently were found to be implicated in familial amyotrophic lateral sclerosis (ALS).3 It was suggested that VCP mutations may account for 1%–2% of familial ALS cases.3 Whether VCP mutations also contribute to sporadic ALS (SALS), however, has not yet been studied. Here, we report the identification of a novel p.Ile151Val mutation in VCP in a patient of African American descent with SALS. ### Case report. In the course of screening patients with ALS ascertained by the ALS Center at Mayo Clinic Florida (MCF) for mutations in the known ALS genes ( SOD1 , TARDBP , FUS , OPTN , and VCP ), we identified an African American patient with the c.451A>G mutation in exon 5 of VCP predicted to result in the p.Ile151Val substitution. Mutations were excluded in all other exons and genes analyzed in this patient. The VCP p.Ile151Val mutation was not previously reported in dbSNP or the 1000 Genomes databases and genotyping using a custom-designed ABI Taqman assay excluded this mutation from 407 healthy African American controls obtained from MCF (n = 317) and the Coriell Institute for Medical Research (n …
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".