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http://hdl.handle.net/10261/11791
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Alías, Laura | - |
dc.contributor.author | Bernal, Sara | - |
dc.contributor.author | Fuentes Prior, Pablo | - |
dc.contributor.author | Barceló, María Jesús | - |
dc.contributor.author | Also, Eva | - |
dc.contributor.author | Martínez-Hernández, Rebeca | - |
dc.contributor.author | Rodríguez-Álvarez, Francisco J. | - |
dc.contributor.author | Martín, Yolanda | - |
dc.contributor.author | Aller, Elena | - |
dc.contributor.author | Grau, Elena | - |
dc.contributor.author | Peciña, Ana | - |
dc.contributor.author | Antiñolo, Guillermo | - |
dc.contributor.author | Galán, Enrique | - |
dc.contributor.author | Rosa, Alberto L. | - |
dc.contributor.author | Fernández-Burriel, Miguel | - |
dc.contributor.author | Borrego, Salud | - |
dc.contributor.author | Millán, José M. | - |
dc.contributor.author | Hernández-Chico, Concepción | - |
dc.contributor.author | Baiget, Montserrat | - |
dc.contributor.author | Tizzano, Eduardo F. | - |
dc.date.accessioned | 2009-03-23T12:04:51Z | - |
dc.date.available | 2009-03-23T12:04:51Z | - |
dc.date.issued | 2009-02 | - |
dc.identifier.citation | Human Genetics 125(1): 29-39 (2009) | en_US |
dc.identifier.issn | 0340-6717 | - |
dc.identifier.uri | http://hdl.handle.net/10261/11791 | - |
dc.description | 11 pages, 2 figures, 3 tables.-- PMID: 19050931 [PubMed].-- Available online Dec 3, 2008. | en_US |
dc.description.abstract | Spinal muscular atrophy (SMA) is caused by mutations in the SMN1 gene. We have studied the molecular pathology of SMA in 745 unrelated Spanish patients using PCR-RFLP, SMN gene dosage analysis, linkage studies, long-range PCR and direct sequencing. Our systematic approach allowed us to complete genetic testing and risk assessment in 736 SMA patients (98.8%). Females were more frequently affected by the acute form of the disease (type I), whereas chronic forms (type II–III) predominated in males (p < 0.008). Absence of the SMN1 gene was detected in 671 patients (90%), and hybrid SMN1–SMN2 genes were observed in 37 cases (5%). Furthermore, we detected 13 small mutations in 28 patients (3.8%), four of which were previously identified in other populations (c.91dupT; c.770_780dup11; p.Tyr272Cys and p.Thr274Ile), while five mutations were found to date only in Spanish patients (c.399_402delAGAG, p.Ile116Phe, p.Gln136Glu, c.740dupC and c.834+2T>G). The c.399_402delAGAG mutation accounted for 1.9% of all Spanish SMA patients. Finally, we discovered four novel mutations: c.312dupA, c.411delT, p.Trp190X and p.Met263Thr. Our results confirm that most SMA cases are due to large genetic rearrangements in the repetitive region of the SMA locus, resulting in absence-dysfunction of the SMN1 gene. By contrast, ancestrally inherited small mutations are responsible for only a small number of cases. Four prevalent changes in exons 3 and 6 (c.399_402delAGAG; c.770_780dup11; p.Tyr272Cys; p.Thr274Ile) accounted for almost 70% of our patients with these subtle mutations. An SMN–SMN dimer model featuring tight hydrophobic-aromatic interactions is proposed to explain the impact of mutations at the C-terminal end of the protein. | en_US |
dc.description.sponsorship | This work was supported by CIBERER (to L.A. and E. Aller), GENAME Project (to S. Bernal, R.M.H., F.J.M.A., E.G. and A.P.), and FIS05-2416 (to E. Also); Grants: FIS 05-2416 (E.F.T.) and GENAME Project (E.F.T., C·H.C., J.M.M., S. Borrego, J.C., M.R.) We wish to thank the consenting parents and patients who made this study possible. | en_US |
dc.format.extent | 821264 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | en_US |
dc.publisher | Springer Nature | en_US |
dc.rights | closedAccess | en_US |
dc.title | Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene | en_US |
dc.type | artículo | en_US |
dc.identifier.doi | 10.1007/s00439-008-0598-1 | - |
dc.description.peerreviewed | Peer reviewed | en_US |
dc.relation.publisherversion | http://dx.doi.org/10.1007/s00439-008-0598-1 | en_US |
dc.identifier.e-issn | 1432-1203 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | none | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
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