{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:57:25Z","timestamp":1782230245290,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T00:00:00Z","timestamp":1594771200000},"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":["Human Mutation"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>PITX1 is a homeobox transcription factor essential for hindlimb morphogenesis. Two <jats:italic>PITX1<\/jats:italic>\u2010related human disorders have been reported to date: <jats:italic>PITX1<\/jats:italic> ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a \u201clower limb\u201d appearance; <jats:italic>PITX1<\/jats:italic> deletions or missense variation cause a syndromic picture including clubfoot, tibial hemimelia, and preaxial polydactyly. We report two novel <jats:italic>PITX1<\/jats:italic> missense variants, altering PITX1 transactivation ability, in three individuals from two unrelated families showing a distinct recognizable autosomal dominant syndrome, including first branchial arch, pelvic, patellar, and male genital abnormalities. This syndrome shows striking similarities with the <jats:italic>Pitx1<\/jats:italic>\u2212\/\u2212 mouse model. A partial phenotypic overlap is also observed with Ischiocoxopodopatellar syndrome caused by <jats:italic>TBX4<\/jats:italic> haploinsufficiency, and with the phenotypic spectrum caused by <jats:italic>SOX9<\/jats:italic> anomalies, both genes being PITX1 downstream targets. Our study findings expand the spectrum of <jats:italic>PITX1<\/jats:italic>\u2010related disorders and suggest a common pattern of developmental abnormalities in disorders of the <jats:italic>PITX1\u2013TBX4\u2013SOX9<\/jats:italic> signaling pathway.<\/jats:p>","DOI":"10.1002\/humu.24070","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T14:18:24Z","timestamp":1593440304000},"page":"1499-1506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mandibular\u2010pelvic\u2010patellar syndrome is a novel <i>PITX1<\/i>\u2010related disorder due to alteration of PITX1 transactivation ability"],"prefix":"10.1155","volume":"41","author":[{"given":"Godelieve","family":"Morel","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Centre de comp\u00e9tences Anomalies du D\u00e9veloppement CHU de Nice Nice France"},{"name":"Service de G\u00e9n\u00e9tique, Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Centre de Comp\u00e9tences Maladies Osseuses Constitutionnelles, Hospices Civils de Lyon Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Duhamel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Boussion","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Fr\u00e9nois","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetan","family":"Lesca","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Centre de Comp\u00e9tences Maladies Osseuses Constitutionnelles, Hospices Civils de Lyon Bron France"},{"name":"INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-0981","authenticated-orcid":false,"given":"Nicolas","family":"Chatron","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Centre de Comp\u00e9tences Maladies Osseuses Constitutionnelles, Hospices Civils de Lyon Bron France"},{"name":"INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Labalme","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, Centre de R\u00e9f\u00e9rence Anomalies du D\u00e9veloppement et Centre de Comp\u00e9tences Maladies Osseuses Constitutionnelles, 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