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dc.contributor.authorLatorre Pecillera, Ana
dc.contributor.authorGil Salvador, Marta
dc.contributor.authorParenti, Ilaria
dc.contributor.authorLucía Campos, Cristina
dc.contributor.authorTrujillano, Laura
dc.contributor.authorMarcos Alcalde, Íñigo 
dc.contributor.authorArnedo, María
dc.contributor.authorAscaso, Ángela
dc.contributor.authorAyerza‑Casas, Ariadna
dc.contributor.authorAntoñanzas Pérez, Rebeca
dc.contributor.authorGervasini, Cristina
dc.contributor.authorPiccione, María
dc.contributor.authorMarini, Milena
dc.contributor.authorWeber, Axel
dc.contributor.authorKuechler, Alma
dc.contributor.authorBueno‑Lozano, Gloria
dc.contributor.authorGómez‑Puertas, Paulino
dc.contributor.authorKaiser, Frank J.
dc.contributor.authorPié, Juan
dc.date.accessioned2022-02-07T12:25:16Z
dc.date.available2022-02-07T12:25:16Z
dc.date.issued2021
dc.identifier.issn2045-2322spa
dc.identifier.urihttp://hdl.handle.net/10641/2784
dc.description.abstractPostzygotic 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.spa
dc.language.isoengspa
dc.publisherScientific Reportsspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.titleClinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood.spa
dc.typearticlespa
dc.description.versionpost-printspa
dc.rights.accessRightsopenAccessspa
dc.description.extent3237 KBspa
dc.identifier.doi10.1038/s41598-021-94958-zspa
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-021-94958-z#citeasspa


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