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dc.contributor.authorArgente Oliver, Jesús 
dc.contributor.authorFlores, Raquel Z.
dc.contributor.authorGutiérrez-Arumí, Armand
dc.contributor.authorVerma, Bhupendra
dc.contributor.authorMartos Moreno, Gabriel Ángel 
dc.contributor.authorCuscó, I.
dc.contributor.authorOghabian, Ali
dc.contributor.authorChowen, Julie Ann
dc.contributor.authorFrilander, Mikko J.
dc.contributor.authorPérez-Jurado, Luis A.
dc.contributor.otherUAM. Departamento de Pediatríaes_ES
dc.date.accessioned2014-12-03T12:00:51Z
dc.date.available2014-12-03T12:00:51Z
dc.date.issued2014-03-01
dc.identifier.citationEMBO Molecular Medicine 6.3 (2014): 299-306en_US
dc.identifier.issn1757-4676 (print)en
dc.identifier.issn1757-4684 (online)en
dc.identifier.urihttp://hdl.handle.net/10486/662774
dc.description.abstractThe molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequencesen_US
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Science and Innovation with the help of European FEDER funding (FIS PI10/0747 to JA, FIS PI10/2512 to LAPJ), the Network Centers for Biomedical Research on Obesity and Nutrition (CIBERobn) and on Rare Diseases (CIBERER) Instituto Carlos III, Fundación Endocrinología y Nutrición, and Academy of Finland and Sigrid Juselius Foundation (to MJF). Antibodies for U11/U12‐65K protein and the purified U11/U12 di‐snRNP were obtained from Dr Reinhard Lührmann (MPI Göttingen). Cell line transformation was performed at the Spanish National DNA Biobank and exome sequencing was performed at qGenomics Laboratories, S.L.en_US
dc.format.extent8 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isospaen
dc.publisherJohn Wiley & Sons, Incen_US
dc.relation.ispartofEMBO Molecular Medicineen_US
dc.rights© 2014 The Authorsen_US
dc.subject.othermRNA splicingen_US
dc.subject.otherPituitary hypoplasiaen_US
dc.subject.otherU12-type intronsen_US
dc.titleDefective minor spliceosome mRNA processing results in isolated familial growth hormone deficiencyen_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1002/emmm.201303573es_ES
dc.identifier.doi10.1002/emmm.201303573en
dc.identifier.publicationfirstpage299en
dc.identifier.publicationissue3en
dc.identifier.publicationlastpage306en
dc.identifier.publicationvolume6es_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.accessRightsopenAccessen
dc.authorUAMArgente Oliver, Jesús (100008)
dc.authorUAMChowen , Julie Ann (268961)
dc.authorUAMMartos Moreno, Gabriel Ángel (101491)
dc.facultadUAMFacultad de Medicina


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