| Autor: |
Ribacoba Renne, Moris Germán, de Munain Adolfo, Pascual-Pascual Samuel I, Gonzalo Juan F, Esteban Jesús, Gámez Josep, Corao Ana I, Alonso Belén, Díaz Marta, Beetz Christian, Sánchez-Ferrero Elena, Álvarez Victoria, Márquez Celedonio, Rosell Jordi, Marín Rosario, García-Barcina Maria J, del Castillo Emilia, Benito Carmen, Coto Eliecer |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
BMC Neurology, Vol 10, Iss 1, p 89 (2010) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2377 |
| DOI: |
10.1186/1471-2377-10-89 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
