{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:56:47Z","timestamp":1775102207873,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AVIESAN Plan Cancer, R\u00e9gion Bretagne"},{"name":"Agence Nationale de Recherche, University of Rennes 1 and Minist\u00e8re de la Recherche et de l\u2019Enseignement Sup\u00e9rieur"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Sexual development is a complex process relying on numerous genes. Disruptions in some of these genes are known to cause differences of sexual development (DSDs). Advances in genome sequencing allowed the discovery of new genes implicated in sexual development, such as PBX1. We present here a fetus with a new PBX1 NM_002585.3: c.320G&gt;A,p.(Arg107Gln) variant, presenting with severe DSD along with renal and lung malformations. Using CRISPR-Cas9 gene editing on HEK293T cells, we generated a KD cell line for PBX1. The KD cell line showed reduced proliferation and adhesion properties compared with HEK293T cells. HEK293T and KD cells were then transfected plasmids coding either PBX1 WT or PBX1-320G&gt;A (mutant). WT or mutant PBX1 overexpression rescued cell proliferation in both cell lines. RNA-seq analyses showed less than 30 differentially expressed genes, in ectopic mutant-PBX1-expressing cells compared with WT-PBX1. Among them, U2AF1, encoding a splicing factor subunit, is an interesting candidate. Overall, mutant PBX1 seems to have modest effects compared with WT PBX1 in our model. However, the recurrence of PBX1 Arg107 substitution in patients with closely related phenotypes calls for its impact in human diseases. Further functional studies are needed to explore its effects on cellular metabolism.<\/jats:p>","DOI":"10.3390\/genes14020273","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:43:29Z","timestamp":1674182609000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional Assessment of a New PBX1 Variant in a 46,XY Fetus with Severe Syndromic Difference of Sexual Development through CRISPR-Cas9 Gene Editing"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-3999","authenticated-orcid":false,"given":"Laura","family":"Mary","sequence":"first","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire, F-35033 Rennes, France"},{"name":"Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement et Travail)-UMR_S 1085, Universit\u00e9 Rennes 1, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Leclerc","sequence":"additional","affiliation":[{"name":"Inserm U1242, Centre de Lutte Contre le Cancer Eug\u00e8ne Marquis, Universit\u00e9 de Rennes, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Labalme","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Hospices Civils de Lyon, F-69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale","family":"Bellaud","sequence":"additional","affiliation":[{"name":"CNRS, Inserm UMS Biosit, France BioImaging, Core Facility H2P2 Rennes, Universit\u00e9 Rennes 1, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-4124","authenticated-orcid":false,"given":"S\u00e9verine","family":"Mazaud-Guittot","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement et Travail)-UMR_S 1085, Universit\u00e9 Rennes 1, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Dr\u00e9ano","sequence":"additional","affiliation":[{"name":"CNRS, UMR 6290 IGDR BIOSIT, Molecular Bases of Tumorigenesis, Universit\u00e9 Rennes 1, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Evrard","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement et Travail)-UMR_S 1085, Universit\u00e9 Rennes 1, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Bigand","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomie Pathologique, H\u00f4pital Pontchaillou, CHU Rennes, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Cauchoix","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomie Pathologique, H\u00f4pital Pontchaillou, CHU Rennes, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Loget","sequence":"additional","affiliation":[{"name":"Service d\u2019Anatomie Pathologique, H\u00f4pital Pontchaillou, CHU Rennes, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lokchine","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Cluzeau","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-671X","authenticated-orcid":false,"given":"David","family":"Gilot","sequence":"additional","affiliation":[{"name":"Inserm U1242, Centre de Lutte Contre le Cancer Eug\u00e8ne Marquis, Universit\u00e9 de Rennes, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc-Antoine","family":"Belaud-Rotureau","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire, F-35033 Rennes, France"},{"name":"Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement et Travail)-UMR_S 1085, Universit\u00e9 Rennes 1, F-35033 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-0261","authenticated-orcid":false,"given":"Sylvie","family":"Jaillard","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de 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