117324 20230706131410.0 doi 10.1038/s41598-021-94958-z sideral 125103 ART-2021-125103 eng Latorre-Pellicer, Ana Universidad de Zaragoza (orcid)0000-0002-4703-6620 Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood 2021 Access copy available to the general public Unrestricted Postzygotic 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. info:eu-repo/grantAgreement/ES/DGA/B32-17R info:eu-repo/grantAgreement/ES/DGA/B32-20R info:eu-repo/grantAgreement/ES/FIS/PI19-01860 info:eu-repo/grantAgreement/ES/ISCIII/PI19-01860 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.997 2021 MULTIDISCIPLINARY SCIENCES 19 / 74 = 0.257 2021 Q2 T1 1.005 2021 Multidisciplinary 2021 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Gil-Salvador, Marta Universidad de Zaragoza (orcid)0000-0001-6858-1575 Parenti, Ilaria Lucia-Campos, Cristina Trujillano, Laura Marcos-Alcalde, Iñigo Arnedo, María Universidad de Zaragoza (orcid)0000-0001-9962-2157 Ascaso, Ángela Ayerza-Casas, Ariadna (orcid)0000-0002-0023-8137 Antoñanzas-Pérez, Rebeca Universidad de Zaragoza Gervasini, Cristina Piccione, Maria Mariani, Milena Weber, Axel Kanber, Deniz Kuechler, Alma Munteanu, Martin Khuller, Katharina Bueno-Lozano, Gloria Universidad de Zaragoza (orcid)0000-0002-0902-387X Puisac, Beatriz Universidad de Zaragoza (orcid)0000-0003-0170-7326 Gómez-Puertas, Paulino Selicorni, Angelo Kaiser, Frank J. Ramos, Feliciano J. Universidad de Zaragoza (orcid)0000-0002-5732-2209 Pié, Juan Universidad de Zaragoza (orcid)0000-0003-3203-6254 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1012 X Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Proy. investigación DUA 1011 670 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Pediatría 11 (2021), 15459 [11 pp.] Sci. rep. (Nat. Publ. Group) Scientific reports (Nature Publishing Group) 2045-2322 3269090 http://zaguan.unizar.es/record/117324/files/texto_completo.pdf Versión publicada 2526142 http://zaguan.unizar.es/record/117324/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117324 articulos driver 2023-07-06-12:20:47 ARTICLE