The Genetic Landscape of Hereditary Spastic Paraplegia in Greece
Hereditary spastic paraplegia (HSP) is a neurogenetic disorder characterized by progressive, length-dependent degeneration of the upper motor neurons. We investigated 112 Greek HSP index cases collected over more than 25 years from all regions of the country, using a combination of next generation sequencing and multiplex ligation-dependent probe amplification. In total, we identified a causative variant in 68 patients, corresponding to a diagnostic yield of 60.7%. The diagnostic yield was 62.8% in autosomal dominant HSP, 77.8% in autosomal recessive HSP and 50.0% in sporadic cases. We identified 7 novel causative variants in SPAST, SPG7, and CYP7B1. We found causative variants in a total of 18 different genes. The most commonly involved genes, affecting more than one family, were SPAST (25.0%), SPG11 (12.5%), CYP7B1 (3.6%), SPG7 (3.6%), KIF5A (2.7%), ABCD1 (1.8%) and PSEN1 (1.8%). Variants in ATL1, REEP1, BSCL2, PLP1, WASCHC5, AP5Z1, CYP27A1, SOD1, POLR3A, GFAP and ARG1 were identified in single families. This study presents a comprehensive overview of the phenotypic and genotypic spectrum of HSP in the Greek population, expanding previous data, and contributing to the characterisation of further pathogenic variants linked to HSP.
Authors
- Charalampos Voudommatis
- David S. Lynch (ORCID: https://orcid.org/0000-0003-0615-7159)
- Georgia Karadima (ORCID: https://orcid.org/0000-0001-7003-5717)
- Georgia Xiromerisiou (ORCID: https://orcid.org/0000-0001-7162-3588)
- Efthimios Dardiotis (ORCID: https://orcid.org/0000-0003-2957-641X)
- Zoi Kontogeorgiou (ORCID: https://orcid.org/0000-0002-9796-8178)
- Ioannis Zaganas (ORCID: https://orcid.org/0000-0002-0774-5772)
- Chrysoula Koniari
- Minas Drakos (ORCID: https://orcid.org/0000-0001-7384-1861)
- Kristina Zhelcheska
- Henry Houlden (ORCID: https://orcid.org/0000-0002-2866-7777)
- Μάριος Πάνας
- Reza Maroofian
- Georgios Koutsis (ORCID: https://orcid.org/0000-0002-8980-8377)
- Leonidas Stefanis
- Rahema Mohammad
- Chrisoula Kartanou
- Nikolaos Ragazos
- Ehsan Barkhordari
Institutions
- University of Crete (GR)
- University of Thessaly (GR)
- National and Kapodistrian University of Athens (GR)
- MIND Research Institute (US)
- University Hospital of Larissa (GR)
- Nicolae Testemițanu State University of Medicine and Pharmacy (MD)
- UCL Biomedical Research Centre (GB)
- Eginition Hospital (GR)
- National Hospital for Neurology and Neurosurgery (GB)
- University College London (GB)
Publication Details
- Journal
- Clinical Genetics
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1111/cge.70113
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Spastic Paraplegia Foundation
- Multiple System Atrophy Coalition
- Hellenic Academic Libraries Link
- National Institute for Health and Care Research
- Ataxia UK
- Guarantors of Brain
- University College London
- Rosetrees Trust
- National and Kapodistrian University of Athens
- Genesis Pharma
- Koning Boudewijnstichting
- National Institutes of Health
- Medical Research Council