Loss‐of‐Function Variants in <scp> <i>CPT1C</i> </scp> : No Support for a Causal Role in Hereditary Spastic Paraplegia
Bibliographic record
Abstract
BACKGROUND: Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders characterized by lower-limb spasticity. Pathogenic variants in CPT1C have been implicated in HSP. OBJECTIVE: The objective of this study was to assess whether CPT1C loss-of-function (LOF) variants are causally associated with HSP. METHODS: We analyzed whole-genome sequencing data from UK Biobank (UKBB), whole-exome sequencing data from a Canadian HSP cohort (Can-HSP), and genetic data from the GENESIS cohort-a large international cohort of patients with rare hereditary diseases, including HSP. RESULTS: Among >170 CPT1C LOF carriers in the UKBB (n = 150,119), none exhibited HSP phenotypes. Among 585 HSP patients from Can-HSP, we did not find patients with CPT1C LOF variants. In the GENESIS cohort (n = 21,217), three individuals carrying CPT1C LOF variants were also diagnosed with HSP; however, all three also carry pathogenic variants in established HSP-associated genes. CONCLUSIONS: Our study does not support a causal role for CPT1C LOF variants in HSP. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 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 source (direct Gemma or distilled Codex), 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".