RT Journal Article
T1 Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.
A1 Alvarez, Victoria
A1 Sánchez-Ferrero, Elena
A1 Beetz, Christian
A1 Díaz, Marta
A1 Alonso, Belén
A1 Corao, Ana I
A1 Gámez, Josep
A1 Esteban, Jesús
A1 Gonzalo, Juan F
A1 Pascual-Pascual, Samuel I
A1 López de Munain, Adolfo
A1 Moris, Germán
A1 Ribacoba, Renne
A1 Márquez, Celedonio
A1 Rosell, Jordi
A1 Marín, Rosario
A1 García-Barcina, Maria J
A1 Castillo, Emilia Del
A1 Benito, Carmen
A1 Coto, Eliecer
K1 Análisis de mutaciones del ADN
K1 GTP fosfohidrolasas
K1 Proteínas de unión al GTP
K1 Genotipo
K1 Paraplejía espástica hereditaria
K1 Adenosina trifosfatasas
AB BACKGROUNDHereditary 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.METHODSWe defined the SPAST and ATL1 mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype).RESULTSWe 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.CONCLUSIONSIn 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.
PB BioMed Central
YR 2010
FD 2010-10-08
LK http://hdl.handle.net/10668/1315
UL http://hdl.handle.net/10668/1315
LA en
NO Alvarez V, Sánchez-Ferrero E, Beetz C, Díaz 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; 10:89
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 9, 2025