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BMC Neurology
Published in: BMC Neurology 1/2010

Open Access 01-12-2010 | Research article

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia

Authors: Victoria Álvarez, Elena Sánchez-Ferrero, Christian Beetz, Marta Díaz, Belén Alonso, Ana I Corao, Josep Gámez, Jesús Esteban, Juan F Gonzalo, Samuel I Pascual-Pascual, Adolfo López de Munain, Germán Moris, Renne Ribacoba, Celedonio Márquez, Jordi Rosell, Rosario Marín, Maria J García-Barcina, Emilia del Castillo, Carmen Benito, Eliecer Coto, the group for the study of the genetics of Spastic Paraplegia*

Published in: BMC Neurology | Issue 1/2010

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Abstract

Background

Hereditary Spastic Paraplegias (HSP) are characterized by progressive spasticity and weakness of the lower limbs. At least 45 loci have been identified in families with autosomal dominant (AD), autosomal recessive (AR), or X-linked hereditary patterns. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes would account for about 50% of the ADHSP cases.

Methods

We defined the SPAST and ATL1 mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype).

Results

We found 50 SPAST mutations (including two large deletions) in 54 patients and 7 ATL1 mutations in 11 patients. A total of 33 of the SPAST and 3 of the ATL1 were new mutations. A total of 141 (31%) were familial cases, and we found a higher frequency of mutation carriers among these compared to apparently sporadic cases (38% vs. 5%). Five of the SPAST mutations were predicted to affect the pre-mRNA splicing, and in 4 of them we demonstrated this effect at the cDNA level. In addition to large deletions, splicing, frameshifting, and missense mutations, we also found a nucleotide change in the stop codon that would result in a larger ORF.

Conclusions

In a large cohort of Spanish patients with spastic paraplegia, SPAST and ATL1 mutations were found in 15% of the cases. These mutations were more frequent in familial cases (compared to sporadic), and were associated with heterogeneous clinical manifestations.
Appendix
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Metadata
Title
Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia
Authors
Victoria Álvarez
Elena Sánchez-Ferrero
Christian Beetz
Marta Díaz
Belén Alonso
Ana I Corao
Josep Gámez
Jesús Esteban
Juan F Gonzalo
Samuel I Pascual-Pascual
Adolfo López de Munain
Germán Moris
Renne Ribacoba
Celedonio Márquez
Jordi Rosell
Rosario Marín
Maria J García-Barcina
Emilia del Castillo
Carmen Benito
Eliecer Coto
the group for the study of the genetics of Spastic Paraplegia*
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2010
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-10-89

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