Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/11791
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Mutation update of spinal muscular atrophy in Spain: molecular characterization of 745 unrelated patients and identification of four novel mutations in the SMN1 gene |
Autor: | Alías, Laura; Bernal, Sara; Fuentes Prior, Pablo; Barceló, María Jesús; Also, Eva; Martínez-Hernández, Rebeca; Rodríguez-Álvarez, Francisco J.; Martín, Yolanda; Aller, Elena; Grau, Elena; Peciña, Ana CSIC ORCID; Antiñolo, Guillermo CSIC ORCID; Galán, Enrique; Rosa, Alberto L.; Fernández-Burriel, Miguel; Borrego, Salud CSIC ORCID; Millán, José M.; Hernández-Chico, Concepción; Baiget, Montserrat; Tizzano, Eduardo F. | Fecha de publicación: | feb-2009 | Editor: | Springer Nature | Citación: | Human Genetics 125(1): 29-39 (2009) | Resumen: | 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. | Descripción: | 11 pages, 2 figures, 3 tables.-- PMID: 19050931 [PubMed].-- Available online Dec 3, 2008. | Versión del editor: | http://dx.doi.org/10.1007/s00439-008-0598-1 | URI: | http://hdl.handle.net/10261/11791 | DOI: | 10.1007/s00439-008-0598-1 | ISSN: | 0340-6717 | E-ISSN: | 1432-1203 |
Aparece en las colecciones: | (IBIS) Artículos (CIC) Artículos |
Mostrar el registro completo
CORE Recommender
SCOPUSTM
Citations
142
checked on 20-abr-2024
WEB OF SCIENCETM
Citations
109
checked on 27-feb-2024
Page view(s)
461
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.