{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNIPBL is a critical regulator of genome organization through its essential role as the cohesin‐loading factor. By binding to chromatin at specific sites, NIPBL facilitates the dynamic loading and unloading of cohesin complexes, thereby promoting the ATPase‐driven loop extrusion process that underpins sister chromatid cohesion and higher‐order chromatin architecture. This fundamental molecular activity not only ensures accurate chromosome segregation during cell division but also establishes a platform for fine‐tuning gene regulation. Several studies have demonstrated that NIPBL influences enhancer–promoter interactions and directly contributes to chromatin looping independent of core cohesin components. In addition, mapping of interaction domains—such as those between NIPBL and MAU2—supports its role in initiating cohesin deposition onto DNA and coordinating its function during early S phase and subsequent replication events."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cohesin loading, NIPBL is instrumental in regulating transcription and ensuring genome stability. By occupying promoter‐proximal regions and coordinating with specific transcription factors—such as BRD4—it helps mediate enhancer‐dependent gene expression and modulates chromatin decompaction. Moreover, studies have shown that NIPBL is recruited to DNA damage sites through distinct domains and interactors, thereby influencing double‐strand break repair pathways and cellular stress responses. This interplay with transcriptional and repair machinery underscores a broader function for NIPBL in shaping the epigenetic landscape and maintaining proper gene expression programs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDefects in NIPBL function have profound developmental and clinical consequences. Heterozygous loss‐of‐function mutations in NIPBL are the major cause of Cornelia de Lange syndrome (CdLS), a multisystem disorder characterized by growth retardation, limb malformations, cognitive impairment, and various organ anomalies. NIPBL mutations have also been implicated in other neurodevelopmental disorders and may contribute to genomic instability observed in certain cancers. In-depth clinical studies reveal that the severity of CdLS phenotypes correlates with the extent of NIPBL dysfunction, and mosaicism for NIPBL mutations further complicates genotype–phenotype relationships. Together, these findings highlight NIPBL’s dual role as a master regulator of chromatin structure and gene expression during development, and as a guardian of genome integrity whose disruption can lead to diverse pathological states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ian D Krantz, Jennifer McCallum, Cheryl DeScipio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1364"}], "href": "https://doi.org/10.1038/ng1364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15146186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15146186"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jacqueline Schoumans, Josephine Wincent, Michela Barbaro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ejhg.5201737"}], "href": "https://doi.org/10.1038/sj.ejhg.5201737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17106445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17106445"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jinglan Liu, Zhe Zhang, Masashige Bando, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional dysregulation in NIPBL and cohesin mutant human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.1000119"}], "href": "https://doi.org/10.1371/journal.pbio.1000119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19468298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19468298"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jessica Zuin, Vedran Franke, Wilfred F J van Ijcken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A cohesin-independent role for NIPBL at promoters provides insights in CdLS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1004153"}], "href": "https://doi.org/10.1371/journal.pgen.1004153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24550742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24550742"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "James Rhodes, Davide Mazza, Kim Nasmyth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Scc2/Nipbl hops between chromosomal cohesin rings after loading."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.30000"}], "href": "https://doi.org/10.7554/eLife.30000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28914604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28914604"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ge Zheng, Mohammed Kanchwala, Chao Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MCM2-7-dependent cohesin loading during S phase promotes sister-chromatid cohesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.33920"}], "href": "https://doi.org/10.7554/eLife.33920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29611806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29611806"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Benedikt W Bauer, Iain F Davidson, Daniel Canena, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cohesin mediates DNA loop extrusion by a \"swing and clamp\" mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2021.09.016"}], "href": "https://doi.org/10.1016/j.cell.2021.09.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34624221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34624221"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lorenzo Rinaldi, Gregory Fettweis, Sohyoung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.abj8360"}], "href": "https://doi.org/10.1126/sciadv.abj8360"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35353576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35353576"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Dácil Alonso-Gil, Ana Cuadrado, Daniel Giménez-Llorente, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-36900-7"}], "href": "https://doi.org/10.1038/s41467-023-36900-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36898992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36898992"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Leisha D Nolen, Shelagh Boyle, Morad Ansari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regional chromatin decompaction in Cornelia de Lange syndrome associated with NIPBL disruption can be uncoupled from cohesin and CTCF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt265"}], "href": "https://doi.org/10.1093/hmg/ddt265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23760082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23760082"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Kobe C Yuen, Baoshan Xu, Ian D Krantz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIPBL Controls RNA Biogenesis to Prevent Activation of the Stress Kinase PKR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.12.012"}], "href": "https://doi.org/10.1016/j.celrep.2015.12.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26725122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26725122"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Huanhuan Zhou, Lei Zheng, Kongbeng Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of Cohesin Loading Factor Nipped-B-Like Protein (NIPBL) Induces Cell Cycle Arrest, Apoptosis, and Autophagy of Breast Cancer Cell Lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/msm.906583"}], "href": "https://doi.org/10.12659/msm.906583"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28987049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28987049"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jason A Mills, Pamela S Herrera, Maninder Kaur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIPBL"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+/-"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " haploinsufficiency reveals a constellation of transcriptome disruptions in the pluripotent and cardiac states."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-19173-9"}], "href": "https://doi.org/10.1038/s41598-018-19173-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29348408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29348408"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Z A Bhuiyan, M Klein, P Hammond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2005.038240"}], "href": "https://doi.org/10.1136/jmg.2005.038240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16236812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16236812"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "A Selicorni, S Russo, C Gervasini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2007.00832.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2007.00832.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17661813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17661813"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Thomas D Barber, Kirk McManus, Karen W Y Yuen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0712384105"}], "href": "https://doi.org/10.1073/pnas.0712384105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18299561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18299561"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "J Yan, F Zhang, E Brundage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2008.062471"}], "href": "https://doi.org/10.1136/jmg.2008.062471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19052029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19052029"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Juan Pié, María Concepción Gil-Rodríguez, Milagros Ciero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.33348"}], "href": "https://doi.org/10.1002/ajmg.a.33348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20358602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20358602"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Magdalena Ratajska, Jolanta Wierzba, Davut Pehlivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cornelia de Lange syndrome case due to genomic rearrangements including NIPBL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2010.08.002"}], "href": "https://doi.org/10.1016/j.ejmg.2010.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20727427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20727427"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Silvia Russo, Maura Masciadri, Cristina Gervasini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intragenic and large NIPBL rearrangements revealed by MLPA in Cornelia de Lange patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2012.7"}], "href": "https://doi.org/10.1038/ejhg.2012.7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22353942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22353942"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Alina Kuzniacka, Jolanta Wierzba, Magdalena Ratajska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectrum of NIPBL gene mutations in Polish patients with Cornelia de Lange syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13353-012-0126-9"}], "href": "https://doi.org/10.1007/s13353-012-0126-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23254390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23254390"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Sylvia A Huisman, Egbert J W Redeker, Saskia M Maas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High rate of mosaicism in individuals with Cornelia de Lange syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2012-101477"}], "href": "https://doi.org/10.1136/jmedgenet-2012-101477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23505322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23505322"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "A Pistocchi, G Fazio, A Cereda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2013.371"}], "href": "https://doi.org/10.1038/cddis.2013.371"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24136230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24136230"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "María E Teresa-Rodrigo, Juliane Eckhold, Beatriz Puisac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of NIPBL physiological splice variants and eight splicing mutations in patients with Cornelia de Lange syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms150610350"}], "href": "https://doi.org/10.3390/ijms150610350"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24918291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24918291"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Diana Braunholz, Carolin Obieglo, Ilaria Parenti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hidden mutations in Cornelia de Lange syndrome limitations of sanger sequencing in molecular diagnostics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22685"}], "href": "https://doi.org/10.1002/humu.22685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25196272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25196272"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Weizhen Xu, Yinyin Ying, Lihong Shan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-015-0503-3"}], "href": "https://doi.org/10.1186/s12967-015-0503-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25963978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25963978"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "A Jeremy Willsey, Thomas V Fernandez, Dongmei Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De Novo Coding Variants Are Strongly Associated with Tourette Disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2017.04.024"}], "href": "https://doi.org/10.1016/j.neuron.2017.04.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28472652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28472652"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Sylvia Huisman, Paul A Mulder, Egbert Redeker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phenotypes and genotypes in individuals with SMC1A variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38279"}], "href": "https://doi.org/10.1002/ajmg.a.38279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28548707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28548707"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Gabrielle Olley, Morad Ansari, Hemant Bengani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-018-0042-y"}], "href": "https://doi.org/10.1038/s41588-018-0042-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29379197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29379197"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Felix D Weiss, Lesly Calderon, Yi-Fang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal genes deregulated in Cornelia de Lange Syndrome respond to removal and re-expression of cohesin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-23141-9"}], "href": "https://doi.org/10.1038/s41467-021-23141-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34006846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34006846"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Ana Latorre-Pellicer, Marta Gil-Salvador, Ilaria Parenti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-94958-z"}], "href": "https://doi.org/10.1038/s41598-021-94958-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34326454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34326454"}]}]}]}