{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:08:01Z","timestamp":1775254081511,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2022,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>PBX1<\/jats:italic> encodes the pre\u2010B cell leukemia factor 1, a Three Amino acid Loop Extension (TALE) transcription factor crucial to regulate basic developmental processes. <jats:italic>PBX1<\/jats:italic> loss\u2010of\u2010function variants have been initially described in association with renal malformations in both isolated and syndromic forms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>Herein, we report a male infant presenting multiple organ malformations (cleidosternal dysostosis, micrognathia, left lung hypoplasia, wide interatrial defect, pulmonary hypertension, total anomalous pulmonary venous return, intestinal malrotation) and carrying the heterozygous de novo c.868C\u2009&gt;\u2009T (p.Arg290Trp) variant in <jats:italic>PBX1<\/jats:italic>. This novel variant affects the highly conserved homeodomain of the protein, leading to a non\u2010conservative substitution and consequently altering its tridimensional structure and DNA\u2010binding capacity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>So far, <jats:italic>PBX1<\/jats:italic> has been reported in association with a broad spectrum of renal anomalies. However, given the role of this gene in many different developing processes, whole\u2010exome sequencing can detect mutations in <jats:italic>PBX1<\/jats:italic> even in patients with different phenotypes, not necessarily involving the renal primordium. This report presents a novel <jats:italic>PBX1<\/jats:italic> variant with a predicted strong deleterious effect. The mutation leads to a non\u2010conservative substitution in a very highly conserved domain of the protein, thus altering its tertiary structure and DNA\u2010binding capacity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2065","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T07:15:05Z","timestamp":1656141305000},"page":"674-681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An example of parenchymal renal sparing in the context of complex malformations due to a novel mutation in the <i>PBX1<\/i> gene"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1857-7505","authenticated-orcid":false,"given":"Federica","family":"Ruscitti","sequence":"first","affiliation":[{"name":"DINOGMI University of Genoa  Genoa 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