{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:30:33Z","timestamp":1761766233238,"version":"3.37.3"},"reference-count":41,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T00:00:00Z","timestamp":1501200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2015\u20100783"],"award-info":[{"award-number":["2015\u20100783"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2017,10,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within <jats:italic>NIPBL<\/jats:italic>, <jats:italic>SMC1A<\/jats:italic>, <jats:italic>SMC3<\/jats:italic>, <jats:italic>RAD21<\/jats:italic>, and <jats:italic>HDAC8<\/jats:italic> genes. These genes codify for the \u201ccohesin complex\u201d playing a role in chromatid adhesion, DNA repair and gene expression regulation. The aim of this study was to investigate retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin biopsies from CdLS patients and healthy controls were cultured and derived primary fibroblast cells were treated with RA or dimethyl sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was isolated for quantitative real\u2010time polymerase chain reaction experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We analyzed several components of RA metabolism in a human cell line of kidney fibroblasts (293T), in addition to fibroblasts collected from both <jats:italic>NIPBL<\/jats:italic>\u2010mutated patients and healthy donors, with or without RA treatment. In all cases, <jats:italic>ADH<\/jats:italic> and <jats:italic>RALDH1<\/jats:italic> gene expression was not affected by RA treatment, while <jats:italic>CRABP1<\/jats:italic> was induced. <jats:italic>CRABP2<\/jats:italic> was dramatically upregulated upon RA treatment in healthy donors but not in CdLS patients cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We investigated if CdLS alterations are associated to perturbation of RA signaling. Cells derived from CdLS patients do not respond to RA signaling as efficiently as healthy controls. RA pathway alterations suggest a possible underlying mechanism for several cellular and developmental abnormalities associated with cohesin function. Birth Defects Research 109:1268\u20131276, 2017. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1070","type":"journal-article","created":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T08:36:54Z","timestamp":1501231014000},"page":"1268-1276","source":"Crossref","is-referenced-by-count":4,"title":["Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts"],"prefix":"10.1002","volume":"109","author":[{"given":"Grazia","family":"Fazio","sequence":"first","affiliation":[{"name":"Centro Ricerca M. 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