Expanding Hereditary Spastic Paraplegias Limits: Biallelic <i>SPAST</i> Variants in Cerebral Palsy Mimics
We provide the first evidence of biallelic inheritance in SPAST-related disorders, supported by functional analysis, expanding the clinical spectrum to include moderate-to-severe early-onset encephalopathy. Our findings emphasize the importance of genetic diagnosis in cerebral palsy for prognosis, counseling, and personalized therapy. The identified variants reveal the genetic complexity of SPAST-related disease and suggest a threshold effect of spastin levels in phenotypic variation. Cellular mechanisms such as mitochondrial dynamics and membrane morphology may contribute to pathogenesis and warrant further investigation.
Authors
- Cristina Hernando‐Davalillo (ORCID: https://orcid.org/0000-0002-5811-134X)
- Loreto Martorell (ORCID: https://orcid.org/0000-0003-0898-7332)
- Lluı́s Armengol (ORCID: https://orcid.org/0000-0002-7141-1865)
- Roser Urreizti (ORCID: https://orcid.org/0000-0003-3617-7134)
- Mónica Roldán (ORCID: https://orcid.org/0000-0002-9530-6234)
- C. Ortez (ORCID: https://orcid.org/0000-0001-8187-8103)
- A. Nascimento (ORCID: https://orcid.org/0000-0003-4952-5732)
- Yalda Jamshidi (ORCID: https://orcid.org/0000-0003-0151-6482)
- Gregorio Nolasco (ORCID: https://orcid.org/0000-0002-0365-4793)
- Jordi Muchart (ORCID: https://orcid.org/0000-0003-4702-5072)
- Reza Boostani (ORCID: https://orcid.org/0000-0003-0055-4452)
- Mercedes Serrano (ORCID: https://orcid.org/0000-0002-2056-2428)
- Daniel Natera‐de Benito (ORCID: https://orcid.org/0000-0001-7764-2085)
- Ali Shoeibi (ORCID: https://orcid.org/0000-0002-5987-3290)
- Ehsan Ghayoor Karimiani
- Rocío Jadraque Rodríguez
- Anna Codina (ORCID: https://orcid.org/0000-0003-0673-9087)
- Ioannis Georvasilis
- María Luisa Ramírez Almaraz
Institutions
- Hospital Sant Joan de Déu Barcelona (ES)
- Mashhad University of Medical Sciences (IR)
- St George's, University of London (GB)
- Instituto de Salud Carlos III (ES)
- Novo Nordisk (Finland) (FI)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Sant Joan de Déu Research Foundation (ES)
- Centro Tecnológico del Agua (ES)
- Catalonian Research and Innovation Centre (ES)
- Hospital General Universitario de Alicante Doctor Balmis (ES)
- Cellular Research (United States) (US)
- National Hospital for Neurology and Neurosurgery (GB)
- University College London (GB)
Publication Details
- Journal
- Annals of Clinical and Translational Neurology
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1002/acn3.70206
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00