Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia.
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.
Crippa
Francesca
F
Laboratory of Molecular Biology, IRCCS Eugenio Medea, Via D.L. Monza 20, 23842 Bosisio Parini, Lecco, Italy.
Panzeri
Chris
C
Martinuzzi
Andrea
A
Arnoldi
Alessia
A
Redaelli
Francesca
F
Tonelli
Alessandra
A
Baschirotto
Cinzia
C
Vazza
Giovanni
G
Mostacciuolo
Maria Luisa
ML
Daga
Andrea
A
Orso
Genny
G
Profice
Paolo
P
Trabacca
Antonio
A
D'Angelo
Maria Grazia
MG
Comi
Giacomo Pietro
GP
Galbiati
Sara
S
Lamperti
Costanza
C
Bonato
Sara
S
Pandolfo
Massimo
M
Meola
Giovanni
G
Musumeci
Olimpia
O
Toscano
Antonio
A
Trevisan
Carlo Pietro
CP
Bresolin
Nereo
N
Bassi
Maria Teresa
MT