Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Clinical Genetics
DOI: 10.1111/cge.70113
Authors: Georgios Koutsis, Viorica Chelban, Chrisoula Kartanou, Zoi Kontogeorgiou, Chrysoula Koniari, Nikolaos Ragazos, Charalampos Voudommatis, Kristina Zhelcheska, David S. Lynch, Reza Maroofian, Ehsan Barkhordari, Rahema Mohammad, Ioannis Zaganas, Minas Drakos, Georgia Xiromerisiou, Efthymios Dardiotis, Leonidas Stefanis, Marios Panas, Henry Houlden, Georgia Karadima
Institutions: National and Kapodistrian University of Athens, Eginition Hospital, Nicolae Testemițanu State University of Medicine and Pharmacy, UCL Queen Square Institute of Neurology, University College London, UCL Biomedical Research Centre, University of Crete, University of Thessaly, University Hospital of Larissa
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,980
Funders: Michael J. Fox Foundation for Parkinson's Research, Multiple System Atrophy Trust, 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, Alzheimer’s Research UK, National and Kapodistrian University of Athens, Genesis Pharma, Koning Boudewijnstichting, National Institutes of Health, Medical Research Council
Awards: G1040344645, G2108247150, G2465347136
OpenAlex ID: W4416570906