title: Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Molecular testing facility in Italy.
  
  
  METHODS
  Sixty unrelated Italian patients with pure (n = 50) and complicated (n = 10) HSP.
  
  
  METHODS
  Mutations in SPG4, SPG3A, SPG6, SPG10, and SPG13.
  
  
  RESULTS
  We identified 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.
authors: Laboratory of Molecular Biology, IRCCS Eugenio Medea, Via D.L. Monza 20, 23842 Bosisio Parini, Lecco, Italy.
authors: Francesca
authors: F
authors: Crippa
authors: Chris
authors: C
authors: Panzeri
authors: Andrea
authors: A
authors: Martinuzzi
authors: Alessia
authors: A
authors: Arnoldi
authors: Francesca
authors: F
authors: Redaelli
authors: Alessandra
authors: A
authors: Tonelli
authors: Cinzia
authors: C
authors: Baschirotto
authors: Giovanni
authors: G
authors: Vazza
authors: Maria Luisa
authors: ML
authors: Mostacciuolo
authors: Andrea
authors: A
authors: Daga
authors: Genny
authors: G
authors: Orso
authors: Paolo
authors: P
authors: Profice
authors: Antonio
authors: A
authors: Trabacca
authors: Maria Grazia
authors: MG
authors: D'Angelo
authors: Giacomo Pietro
authors: GP
authors: Comi
authors: Sara
authors: S
authors: Galbiati
authors: Costanza
authors: C
authors: Lamperti
authors: Sara
authors: S
authors: Bonato
authors: Massimo
authors: M
authors: Pandolfo
authors: Giovanni
authors: G
authors: Meola
authors: Olimpia
authors: O
authors: Musumeci
authors: Antonio
authors: A
authors: Toscano
authors: Carlo Pietro
authors: CP
authors: Trevisan
authors: Nereo
authors: N
authors: Bresolin
authors: Maria Teresa
authors: MT
authors: Bassi