Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/13428
Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia
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ISSN: 1471-2377
WOS ID: 000283364700001
Scopus EID: 2-s2.0-77958469481
PMID: 20932283
Embase PUI: L359827832
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Alvarez, Victoria; Sanchez-Ferrero, Elena; Beetz, Christian; Diaz, Marta; Alonso, Belen; Corao, Ana I.; Gamez, Josep; Esteban, Jesus; Gonzalo, Juan F.; Pascual-Pascual, Samuel I.; Lopez de Munain, Adolfo; Moris, German; Ribacoba, Renne; Marquez, Celedonio; Rosell, Jordi; Marin, Rosario; Garcia-Barcina, Maria J.; del Castillo, Emilia; Benito, Carmen; Coto, Eliecer; Grp Study Genetics SpasticPublication date
2010-10-08Document type
research articleCitation
Alvarez V, Sanchez-Ferrero E, Beetz C, Diaz M, Alonso B, Corao AI, et al. Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. BMC Neurol. 2010 Oct 08;10:89.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.
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https://dx.doi.org/10.1186/1471-2377-10-89MeSH
ChildGenotype
Aged
European Continental Ancestry Group
Young Adult
Adult
Adenosine Triphosphatases
GTP Phosphohydrolases
Humans
Child, Preschool
Adolescent
Spastin
Middle Aged
Infant
Membrane Proteins
Phenotype
DNA Mutational Analysis
Spastic Paraplegia, Hereditary
Polymerase Chain Reaction
GTP-Binding Proteins
Pedigree
DeCS
GTP FosfohidrolasasProteínas de Unión al GTP
Paraplejía Espástica Hereditaria
Lactante
Proteínas de la Membrana
Análisis Mutacional de ADN
Grupo de Ascendencia Continental Europea
Adolescente
Adenosina Trifosfatasas
Preescolar
Humanos
Persona de Mediana Edad
Adulto Joven
Anciano
Genotipo
Fenotipo
Niño
Linaje
Espastina
Adulto
Reacción en Cadena de la Polimerasa