| Home > Articles > Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood > MARC |
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
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