000117324 001__ 117324
000117324 005__ 20230706131410.0
000117324 0247_ $$2doi$$a10.1038/s41598-021-94958-z
000117324 0248_ $$2sideral$$a125103
000117324 037__ $$aART-2021-125103
000117324 041__ $$aeng
000117324 100__ $$0(orcid)0000-0002-4703-6620$$aLatorre-Pellicer, Ana$$uUniversidad de Zaragoza
000117324 245__ $$aClinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood
000117324 260__ $$c2021
000117324 5060_ $$aAccess copy available to the general public$$fUnrestricted
000117324 5203_ $$aPostzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families.
000117324 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B32-17R$$9info:eu-repo/grantAgreement/ES/DGA/B32-20R$$9info:eu-repo/grantAgreement/ES/FIS/PI19-01860$$9info:eu-repo/grantAgreement/ES/ISCIII/PI19-01860
000117324 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000117324 590__ $$a4.997$$b2021
000117324 592__ $$a1.005$$b2021
000117324 591__ $$aMULTIDISCIPLINARY SCIENCES$$b19 / 74 = 0.257$$c2021$$dQ2$$eT1
000117324 593__ $$aMultidisciplinary$$c2021$$dQ1
000117324 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000117324 700__ $$0(orcid)0000-0001-6858-1575$$aGil-Salvador, Marta$$uUniversidad de Zaragoza
000117324 700__ $$aParenti, Ilaria
000117324 700__ $$aLucia-Campos, Cristina
000117324 700__ $$aTrujillano, Laura
000117324 700__ $$aMarcos-Alcalde, Iñigo
000117324 700__ $$0(orcid)0000-0001-9962-2157$$aArnedo, María$$uUniversidad de Zaragoza
000117324 700__ $$aAscaso, Ángela
000117324 700__ $$0(orcid)0000-0002-0023-8137$$aAyerza-Casas, Ariadna
000117324 700__ $$aAntoñanzas-Pérez, Rebeca$$uUniversidad de Zaragoza
000117324 700__ $$aGervasini, Cristina
000117324 700__ $$aPiccione, Maria
000117324 700__ $$aMariani, Milena
000117324 700__ $$aWeber, Axel
000117324 700__ $$aKanber, Deniz
000117324 700__ $$aKuechler, Alma
000117324 700__ $$aMunteanu, Martin
000117324 700__ $$aKhuller, Katharina
000117324 700__ $$0(orcid)0000-0002-0902-387X$$aBueno-Lozano, Gloria$$uUniversidad de Zaragoza
000117324 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, Beatriz$$uUniversidad de Zaragoza
000117324 700__ $$aGómez-Puertas, Paulino
000117324 700__ $$aSelicorni, Angelo
000117324 700__ $$aKaiser, Frank J.
000117324 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, Feliciano J.$$uUniversidad de Zaragoza
000117324 700__ $$0(orcid)0000-0003-3203-6254$$aPié, Juan$$uUniversidad de Zaragoza
000117324 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000117324 7102_ $$11012$$2X$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cProy. investigación DUA
000117324 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000117324 773__ $$g11 (2021), 15459 [11 pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322
000117324 8564_ $$s3269090$$uhttps://zaguan.unizar.es/record/117324/files/texto_completo.pdf$$yVersión publicada
000117324 8564_ $$s2526142$$uhttps://zaguan.unizar.es/record/117324/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000117324 909CO $$ooai:zaguan.unizar.es:117324$$particulos$$pdriver
000117324 951__ $$a2023-07-06-12:20:47
000117324 980__ $$aARTICLE