| Title: | Loss-of-Function Variants in CPT1C: No Support for a Causal Role in Hereditary Spastic Paraplegia |
| Journal: | Movement Disorders |
| Published: | 28 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41312619/ |
| DOI: | https://doi.org/10.1002/mds.70144 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mds.70144 |
Publication 17287
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Abstract
BACKGROUND: Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders characterized by lower-limb spasticity. Pathogenic variants in CPT1C have been implicated in HSP.</p>
OBJECTIVE: The objective of this study was to assess whether CPT1C loss-of-function (LOF) variants are causally associated with HSP.</p>
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.</p>
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.</p>
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.</p>
18 Authors
- Rui Zhu
- Lang Liu
- Mehrdad A. Estiar
- Farnaz Asayesh
- Jamil Ahmad
- Meron Teferra
- Grace Yoon
- Mark Tarnopolsky
- Kym M. Boycott
- Nicolas Dupre
- Patrick A. Dion
- Oksana Suchowersky
- Albena Jordanova
- Yi-Chung Lee
- Giovanni Stevanin
- Stephan Zuchner
- Guy A. Rouleau
- Ziv Gan-Or
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