dc.creator | Luzón-Toro, Berta | es |
dc.creator | Fernández, Raquel María | es |
dc.creator | Torroglosa, Ana | es |
dc.creator | Agustín, Juan Carlos de | es |
dc.creator | Méndez-Vidal, Cristina | es |
dc.creator | Segura Ayestarán, Dolores Isabel | es |
dc.creator | Antiñolo Gil, Guillermo | es |
dc.creator | Borrego, Salud | es |
dc.date.accessioned | 2021-04-26T18:50:34Z | |
dc.date.available | 2021-04-26T18:50:34Z | |
dc.date.issued | 2013-01-23 | |
dc.identifier.citation | Luzón-Toro, B., Fernández, R.M., Torroglosa, A., Agustín, J.C.d., Méndez-Vidal, C., Segura Ayestarán, D.I.,...,Borrego, S. (2013). Mutational Spectrum of Semaphorin 3A and Semaphorin 3D Genes in Spanish Hirschsprung patients. PLoS ONE, 8 (1), 54800-. | |
dc.identifier.issn | 1932-6203 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/107869 | |
dc.description.abstract | Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells
along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic colon
segment and functional intestinal obstruction. The RET proto-oncogene is the major gene associated to HSCR with
differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this
pathology. In addition, many other genes have been described to be associated with this pathology, including the
semaphorins class III genes SEMA3A (7p12.1) and SEMA3D (7q21.11) through SNP array analyses and by next-generation
sequencing technologies. Semaphorins are guidance cues for developing neurons implicated in the axonal projections and
in the determination of the migratory pathway for neural-crest derived neural precursors during enteric nervous system
development. In addition, it has been described that increased SEMA3A expression may be a risk factor for HSCR through
the upregulation of the gene in the aganglionic smooth muscle layer of the colon in HSCR patients. Here we present the
results of a comprehensive analysis of SEMA3A and SEMA3D in a series of 200 Spanish HSCR patients by the mutational
screening of its coding sequence, which has led to find a number of potentially deleterious variants. RET mutations have
been also detected in some of those patients carrying SEMAs variants. We have evaluated the A131T-SEMA3A, S598GSEMA3A and E198K-SEMA3D mutations using colon tissue sections of these patients by immunohistochemistry. All mutants
presented increased protein expression in smooth muscle layer of ganglionic segments. Moreover, A131T-SEMA3A also
maintained higher protein levels in the aganglionic muscle layers. These findings strongly suggest that these mutants have
a pathogenic effect on the disease. Furthermore, because of their coexistence with RET mutations, our data substantiate the
additive genetic model proposed for this rare disorder and further support the association of SEMAs genes with HSCR. | es |
dc.description.sponsorship | Instituto de Salud Carlos III (ISCIII), Spain (PI1001290) | es |
dc.description.sponsorship | Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía (CTS-7447) | es |
dc.description.sponsorship | CIBER de Enfermedades Raras is an initiative of the ISCIII, Ministerio de Economía y Competitividad | es |
dc.format | application/pdf | es |
dc.format.extent | 9 | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.relation.ispartof | PLoS ONE, 8 (1), 54800. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Semaphorin | es |
dc.subject | 3A | es |
dc.subject | 3D | es |
dc.subject | Hirschsprung disease | es |
dc.title | Mutational Spectrum of Semaphorin 3A and Semaphorin 3D Genes in Spanish Hirschsprung patients | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Cirugía | es |
dc.relation.projectID | PI1001290 | es |
dc.relation.projectID | CTS-7447 | es |
dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054800 | es |
dc.identifier.doi | 10.1371/journal.pone.0054800 | es |
dc.journaltitle | PLoS ONE | es |
dc.publication.volumen | 8 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 54800 | es |