{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:06:20Z","timestamp":1778717180339,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ulnar mammary syndrome (UMS) results from heterozygous variants in the <jats:italic>TBX3<\/jats:italic> gene and impacts limb, tooth, hair, apocrine gland, and genitalia development. The expressivity of UMS is highly variable with no established genotype\u2013phenotype correlations. <jats:italic>TBX3<\/jats:italic> belongs to the <jats:italic>Tbx<\/jats:italic> gene family, which encodes transcription factors characterized by the presence of a T\u2010box DNA\u2010binding domain. We describe a fetus exhibiting severe upper limb defects and harboring the novel <jats:italic>TBX3<\/jats:italic>:c.400\u2009C\u2009&gt;\u2009T (p.P134S) variant inherited from the mother who remained clinically misdiagnosed until prenatal diagnosis. Literature revision was conducted to uncover the <jats:italic>TBX3<\/jats:italic> clinical and mutational spectrum. Moreover, we generated a <jats:italic>Drosophila<\/jats:italic> humanized model for <jats:italic>TBX3<\/jats:italic> to study the developmental consequences of the p.P134S as well as of other variants targeting different regions of the protein.<\/jats:p><jats:p>Phenotypic analysis in flies, coupled with <jats:italic>in silico<\/jats:italic> modeling on the <jats:italic>TBX3<\/jats:italic> variants, suggested that the c.400\u2009C\u2009&gt;\u2009T is UMS\u2010causing and impacts TBX3 localization. Comparative analyses of the fly phenotypes caused by the expression of all variants, demonstrated that missense changes in the T\u2010box domain affect more significantly TBX3 activity than variants outside this domain. To improve the clinicians' recognition of UMS, we estimated the frequency of the main clinical features of the disease. Core features often present pre\u2010pubertally include defects of the ulna and\/or of ulnar ray, hypoplastic nipples and\/or areolas and, less frequently, genitalia anomalies in young males. These results enhance our understanding of the molecular basis and the clinical spectrum of UMS, shedding light on the functional consequences of <jats:italic>TBX3<\/jats:italic> variants in a developmental context.<\/jats:p>","DOI":"10.1002\/jcp.31440","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T20:49:30Z","timestamp":1727297370000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An inherited TBX3 alteration in a prenatal case of ulnar\u2010mammary syndrome: Clinical assessment and functional characterization in <i>Drosophila melanogaster<\/i>"],"prefix":"10.1002","volume":"239","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0396-7981","authenticated-orcid":false,"given":"Irene","family":"Bottillo","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Experimental Medicine, San Camillo\u2010Forlanini Hospital Sapienza University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"D'Alessandro","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cC. Darwin\u201d Sapienza University of Rome Rome Italy"},{"name":"Istituto Pasteur Italia\u2010Fondazione Cenci Bolognetti Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pia","family":"Ciccone","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Experimental Medicine, San Camillo\u2010Forlanini Hospital Sapienza University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-631X","authenticated-orcid":false,"given":"Gianluca","family":"Cestra","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cC. Darwin\u201d Sapienza University of Rome Rome Italy"},{"name":"Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) Rome Italy"},{"name":"Fondazione Santa Lucia IRCCS, c\/o CERC Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Experimental Medicine, San Camillo\u2010Forlanini Hospital Sapienza University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelina","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Unit of Fetal and Neonatal Pathology, Division of Pathology San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Brancati","sequence":"additional","affiliation":[{"name":"Human Genetics Laboratory, Department of Life, Health and Environmental Sciences University of L'Aquila  Italy"},{"name":"San Raffaele Roma IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Lenzi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-7545","authenticated-orcid":false,"given":"Alessandro","family":"Paiardini","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. 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