{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:41:58Z","timestamp":1792172518210,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Patent Foramen Ovale (PFO) is a common postnatal defect of cardiac atrial septation. A certain degree of familial aggregation has been reported. Animal studies suggest the involvement of the Notch pathway and other cardiac transcription factors (GATA4, TBX20, NKX2-5) in Foramen Ovale closure. This review evaluates the contribution of genetic alterations in PFO development. We systematically reviewed studies that assessed rare and common variants in subjects with PFO. The protocol was registered with PROSPERO and followed MOOSE guidelines. We systematically searched English studies reporting rates of variants in PFO subjects until the 30th of June 2021. Among 1231 studies, we included four studies: two of them assessed the NKX2-5 gene, the remaining reported variants of chromosome 4q25 and the GATA4 S377G variant, respectively. We did not find any variant associated with PFO, except for the rs2200733 variant of chromosome 4q25 in atrial fibrillation patients. Despite the scarceness of evidence so far, animal studies and other studies that did not fulfil the criteria to be included in the review indicate a robust genetic background in PFO. More research is needed on the genetic determinants of PFO.<\/jats:p>","DOI":"10.3390\/genes12121953","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:01:45Z","timestamp":1638738105000},"page":"1953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Genetic Landscape of Patent Foramen Ovale: A Systematic Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-378X","authenticated-orcid":false,"given":"Matteo","family":"Paolucci","sequence":"first","affiliation":[{"name":"Headache and Neurosonology Unit, Neurology, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128 Rome, Italy"},{"name":"Neurology Unit, \u201cM. Bufalini\u201d Hospital, AUSL Romagna, Viale Giovanni Ghirotti, 286, 47521 Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Stroke Unit, AUSL-IRCCS di Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Romoli","sequence":"additional","affiliation":[{"name":"Neurology Unit, \u201cM. Bufalini\u201d Hospital, AUSL Romagna, Viale Giovanni Ghirotti, 286, 47521 Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-2015","authenticated-orcid":false,"given":"Giulia","family":"Amico","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy"},{"name":"DINOGMI-Universite degli Studi di Genova, Largo P. Daneo,3, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-1955","authenticated-orcid":false,"given":"Isabella","family":"Ceccherini","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-0083","authenticated-orcid":false,"given":"Simona","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-628X","authenticated-orcid":false,"given":"Anna","family":"Bersano","sequence":"additional","affiliation":[{"name":"Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Longoni","sequence":"additional","affiliation":[{"name":"Neurology Unit, \u201cM. Bufalini\u201d Hospital, AUSL Romagna, Viale Giovanni Ghirotti, 286, 47521 Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0651-1939","authenticated-orcid":false,"given":"Simona","family":"Sacco","sequence":"additional","affiliation":[{"name":"Neuroscience Section, Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Vernieri","sequence":"additional","affiliation":[{"name":"Headache and Neurosonology Unit, Neurology, Campus Bio-Medico University Hospital, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-9298","authenticated-orcid":false,"given":"Rosario","family":"Pascarella","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, AUSL-IRCCS di Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Valzania","sequence":"additional","affiliation":[{"name":"Neurology Unit, Stroke Unit, AUSL-IRCCS di Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-818X","authenticated-orcid":false,"given":"Marialuisa","family":"Zedde","sequence":"additional","affiliation":[{"name":"Neurology Unit, Stroke Unit, AUSL-IRCCS di Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1161\/CIRCULATIONAHA.104.524371","article-title":"Patent Foramen Ovale and Stroke","volume":"112","author":"Homma","year":"2005","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/ana.24609","article-title":"Transcranial Doppler versus Transthoracic Echocardiography for the Detection of Patent Foramen Ovale in Patients with Cryptogenic Cerebral Ischemia: A Systematic Review and Diagnostic Test Accuracy Meta-Analysis","volume":"79","author":"Katsanos","year":"2016","journal-title":"Ann. 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