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dc.contributor.authorAlías, Laura-
dc.contributor.authorBernal, Sara-
dc.contributor.authorFuentes Prior, Pablo-
dc.contributor.authorBarceló, María Jesús-
dc.contributor.authorAlso, Eva-
dc.contributor.authorMartínez-Hernández, Rebeca-
dc.contributor.authorRodríguez-Álvarez, Francisco J.-
dc.contributor.authorMartín, Yolanda-
dc.contributor.authorAller, Elena-
dc.contributor.authorGrau, Elena-
dc.contributor.authorPeciña, Ana-
dc.contributor.authorAntiñolo, Guillermo-
dc.contributor.authorGalán, Enrique-
dc.contributor.authorRosa, Alberto L.-
dc.contributor.authorFernández-Burriel, Miguel-
dc.contributor.authorBorrego, Salud-
dc.contributor.authorMillán, José M.-
dc.contributor.authorHernández-Chico, Concepción-
dc.contributor.authorBaiget, Montserrat-
dc.contributor.authorTizzano, Eduardo F.-
dc.date.accessioned2009-03-23T12:04:51Z-
dc.date.available2009-03-23T12:04:51Z-
dc.date.issued2009-02-
dc.identifier.citationHuman Genetics 125(1): 29-39 (2009)en_US
dc.identifier.issn0340-6717-
dc.identifier.urihttp://hdl.handle.net/10261/11791-
dc.description11 pages, 2 figures, 3 tables.-- PMID: 19050931 [PubMed].-- Available online Dec 3, 2008.en_US
dc.description.abstractSpinal 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.sponsorshipThis 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.extent821264 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsclosedAccessen_US
dc.titleMutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 geneen_US
dc.typeartículoen_US
dc.identifier.doi10.1007/s00439-008-0598-1-
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://dx.doi.org/10.1007/s00439-008-0598-1en_US
dc.identifier.e-issn1432-1203-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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