Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia

Francesca Crippa, Chris Panzeri, Andrea Martinuzzi, Alessia Arnoldi, Francesca Redaelli, Alessandra Tonelli, Cinzia Baschirotto, Giovanni Vazza, Maria Luisa Mostacciuolo, Andrea Daga, Genny Orso, Paolo Profice, Antonio Trabacca, Maria Grazia D'Angelo, Giacomo Pietro Comi, Sara Galbiati, Costanza Lamperti, Sara Bonato, Massimo Pandolfo, Giovanni MeolaOlimpia Musumeci, Antonio Toscano, Carlo Pietro Trevisan, Nereo Bresolin, Maria Teresa Bassi

Research output: Contribution to journalArticlepeer-review


Background: Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous disorders characterized by progressive spasticity of the lower limbs. Mutations in the SPG4 gene, which encodes spastin protein, are responsible for up to 45% of autosomal dominant cases. Objective: To search for disease-causing mutations in a large series of Italian patients with HSP. Design: Samples of DNA were analyzed by direct sequencing of all exons in SPG4. Samples from a subset of patients were also analyzed by direct sequencing of all exons in SPG3A, SPG6, SPG10, and SPG13. Setting: Molecular testing facility in Italy. Patients: Sixty unrelated Italian patients with pure (n=50) and complicated (n=10) HSP. Main Outcome Measures: Mutations in SPG4, SPG3A, SPG6, SPG10, and SPG13. Results:Weidentified 12 different mutations, 8 of which were novel, in 13 patients. No mutations of any of the other HSP genes tested were found in 15 patients with sporadic pure HSP who did not have mutations in the SPG4 gene. Conclusions: The overall rate of mutation in the SPG4 gene within our sample was 22%, rising to 26% when only patients with pure HSP were considered. The negative result obtained in 15 patients without mutations in SPG4 in whom 4 other genes were analyzed (SPG3A, SPG6, SPG10, and SPG13) indicate that these genes are not frequently mutated in sporadic pure HSP.

Original languageEnglish
Pages (from-to)750-755
Number of pages6
JournalArchives of Neurology
Issue number5
Publication statusPublished - May 2006

ASJC Scopus subject areas

  • Neuroscience(all)


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