000048096 001__ 48096
000048096 005__ 20161006102701.0
000048096 0247_ $$2doi$$a10.1155/2016/8742939
000048096 0248_ $$2sideral$$a93727
000048096 037__ $$aART-2016-93727
000048096 041__ $$aeng
000048096 100__ $$0(orcid)0000-0002-7528-8518$$aTeresa Rodrigo, María Esperanza
000048096 245__ $$aIdentification and Functional Characterization of Two Intronic NIPBL Mutations in Two Patients with Cornelia de Lange Syndrome
000048096 260__ $$c2016
000048096 5060_ $$aAccess copy available to the general public$$fUnrestricted
000048096 5203_ $$aCornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder with a high phenotypic variability including mental retardation, developmental delay, and limb malformations. The genetic causes in about 30% of patients with CdLS are still unknown. We report on the functional characterization of two intronic NIPBL mutations in two patients with CdLS that do not affect a conserved splice-donor or acceptor site. Interestingly, mRNA analyses showed aberrantly spliced transcripts missing exon 28 or 37, suggesting the loss of the branch site by the c.5329-15A>G transition and a disruption of the polypyrimidine by the c.6344del(-13)-(-8) deletion. While the loss of exon 28 retains the reading frame of the NIBPL transcript resulting in a shortened protein, the loss of exon 37 shifts the reading frame with the consequence of a premature stop of translation. Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript. Consistent with our results, this patient shows a more severe phenotype compared to the patient with the aberrant transcript that retains its reading frame. Thus, intronic variants identified by sequencing analysis in CdLS diagnostics should carefully be examined before excluding them as nonrelevant to disease. Copyright
000048096 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B20$$9info:eu-repo/grantAgreement/ES/FIS/PI12-01318
000048096 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000048096 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000048096 700__ $$aEckhold, J.
000048096 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac Uriol, Beatriz$$uUniversidad de Zaragoza
000048096 700__ $$aPozojevic, J.
000048096 700__ $$aParenti, I.
000048096 700__ $$aBaquero-Montoya, C.
000048096 700__ $$0(orcid)0000-0002-9157-1444$$aGil Rodríguez, María Concepción
000048096 700__ $$aBraunholz, D.
000048096 700__ $$aDalski, A.
000048096 700__ $$0(orcid)0000-0001-8457-1377$$aHernández Marcos, María
000048096 700__ $$0(orcid)0000-0002-0023-8137$$aAyerza Casas, Ariadna
000048096 700__ $$0(orcid)0000-0002-8222-1418$$aBernal Ruiz, María Luisa$$uUniversidad de Zaragoza
000048096 700__ $$0(orcid)0000-0002-5732-2209$$aRamos Fuentes, Feliciano Jesús$$uUniversidad de Zaragoza
000048096 700__ $$aWieczorek, D.
000048096 700__ $$aGillessen-Kaesbach, G.
000048096 700__ $$0(orcid)0000-0003-3203-6254$$aPié Juste, Juan$$uUniversidad de Zaragoza
000048096 700__ $$aKaiser, F. J.
000048096 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDepartamento de Farmacología y Fisiología$$cFisiología
000048096 7102_ $$11010$$2670$$aUniversidad de Zaragoza$$bDepartamento de Pediatría, Radiología y Medicina Física$$cPediatría
000048096 7102_ $$11005$$2315$$aUniversidad de Zaragoza$$bDepartamento de Farmacología y Fisiología$$cFarmacología
000048096 773__ $$g2016 (2016), 8742939 [ 8 p.]$$pBioMed res. int.$$tBioMed Research International$$x2314-6133
000048096 8564_ $$s2575610$$uhttp://zaguan.unizar.es/record/48096/files/texto_completo.pdf$$yVersión publicada
000048096 8564_ $$s95339$$uhttp://zaguan.unizar.es/record/48096/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000048096 909CO $$ooai:zaguan.unizar.es:48096$$particulos$$pdriver
000048096 951__ $$a2016-03-03-09:38:23
000048096 980__ $$aARTICLE