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dc.contributor.author
Juanes, Matías Hernan
dc.contributor.author
Guercio, Gabriela Viviana
dc.contributor.author
Marino, Roxana
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Berensztein, Esperanza Beatriz
dc.contributor.author
Warman, Diana Monica
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Ciaccio, Marta
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Gil, Silvia
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Bailez, Marcela
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Rivarola, Marco Aurelio
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Belgorosky, Alicia
dc.date.available
2018-02-06T17:41:04Z
dc.date.issued
2014-07
dc.identifier.citation
Juanes, Matías Hernan; Guercio, Gabriela Viviana; Marino, Roxana; Berensztein, Esperanza Beatriz; Warman, Diana Monica; et al.; Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment; Wiley; Clinical Endocrinology; 82; 5; 7-2014; 704-711
dc.identifier.issn
0300-0664
dc.identifier.uri
http://hdl.handle.net/11336/35795
dc.description.abstract
Background: IGF1R gene mutations have been associated with varying degrees of intrauterine and postnatal growth retardation, and microcephaly. Objective: To identify and characterize IGF1R gene variations in a cohort of 28 Argentinean children suspected of having IGF-1 insensitivity, who were selected on the basis of the association of pre/postnatal growth failure and microcephaly. Methods: The coding sequence and flanking intronic regions of IGF1R gene were amplified and directly sequenced. Functional characterization was performed by two in vitro assays: 1) [Methyl-3H] thymidine incorporation into DNA in fibroblast cell primary cultures from patients and controls treated with IGF-1 for 16-24 h. 2) PI3K/Akt pathway was evaluated with phospho-Akt (Ser473) STAR ELISA Kit (Millipore) in fibroblast cultures from patients and controls stimulated with IGF-1 for 10 min. Prepubertal clinical and GH-IGF-1 axis evaluation was followed up. Results: We identified three novel heterozygous missense mutations in three unrelated patients, de novo p.Arg1256Ser, de novo p.Asn359Tyr and p.Tyr865Cys. In control cells, proliferation assay showed that IGF-1 significantly induced DNA synthesis at 20 h and Akt phosphorylation assay that it significantly stimulated phosphorylation after 10 min (P < 0·05 by anova and Bonferroni Tests). However, no significant increase was observed in any of the three patient fibroblasts in both functional studies. GH therapy growth response in two patients was inconsistent. Conclusion: These variations led to failure of the IGF1R function causing pre- and postnatal growth retardation and microcephaly. Microcephaly should be considered in the evaluation of SGA patients, because it seems to favour the frequency of detection of IGF1R mutations.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Igf1r Mutations
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Prenatal And Postnatal Growth Retardation.
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Microcephalic
dc.subject.classification
Medicina Critica y de Emergencia
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-02-05T20:13:13Z
dc.journal.volume
82
dc.journal.number
5
dc.journal.pagination
704-711
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.description.fil
Fil: Juanes, Matías Hernan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Guercio, Gabriela Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Marino, Roxana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Warman, Diana Monica. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Ciaccio, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Gil, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Bailez, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Clinical Endocrinology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/cen.12555
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/cen.12555/abstract


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