{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:07:24Z","timestamp":1788217644691,"version":"build-2803163510"},"reference-count":26,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK121175,DK122039,DK135032"],"award-info":[{"award-number":["DK121175,DK122039,DK135032"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,9]]},"abstract":"<jats:p>\n                    <jats:italic>PDX1<\/jats:italic>\n                    mutations are associated with multiple forms of diabetes, including syndromic, neonatal, mature onset diabetes of the young (MODY), and type 2 diabetes. Two\n                    <jats:italic>PDX1<\/jats:italic>\n                    missense mutations (Thr151Met and Asn196Thr) were identified in a pediatric female patient that cause permanent neonatal diabetes, pancreas hypoplasia, and a malformed gallbladder. We found that the mouse\n                    <jats:italic>Pdx1<\/jats:italic>\n                    Asn197Thr variant (homologous to human\n                    <jats:italic>PDX1<\/jats:italic>\n                    Asn196Thr), but not\n                    <jats:italic>Pdx1<\/jats:italic>\n                    Thr152Met (homologous to human\n                    <jats:italic>PDX1<\/jats:italic>\n                    Thr151Met), altered its nuclear localization and disrupted the PDX1-ONECUT1 interaction. Neither variant substantially affected PDX1 protein stability, but both reduced PDX1 binding to the\n                    <jats:italic>Pdx1<\/jats:italic>\n                    gene promoter. Importantly, the\n                    <jats:italic>Pdx1<\/jats:italic>\n                    Asn197Thr variant caused pancreas agenesis and reduced enteroendocrine cells in the duodenum in genetically engineered mice, due at least in part to reduced\n                    <jats:italic>Pdx1<\/jats:italic>\n                    promoter binding and disrupted PDX1-ONECUT1 interaction.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189343","type":"journal-article","created":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T14:00:26Z","timestamp":1749391226000},"source":"Crossref","is-referenced-by-count":6,"title":["Neonatal diabetes\u2013associated missense PDX1 variant disrupts chromatin association and protein-protein interaction"],"prefix":"10.1172","volume":"10","author":[{"given":"Xiaodun","family":"Yang","sequence":"first","affiliation":[{"name":"Institute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Zanfardino","sequence":"additional","affiliation":[{"name":"Regional Center for Pediatric Diabetes, Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Schiaffini","sequence":"additional","affiliation":[{"name":"Diabetology and Growth Disorders Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bareket","family":"Daniel","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Haemmerle","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Novella","family":"Rapini","sequence":"additional","affiliation":[{"name":"Diabetology and Growth Disorders Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Regional Center for Pediatric Diabetes, Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Miraglia del Giudice","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Campania \u201cLuigi Vanvitelli,\u201d Caserta CE, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit and Medical Genetics and Rare Disease Research Division, Bambino Ges\u00f9 Children Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Iorio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Mucciolo","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cianfarani","sequence":"additional","affiliation":[{"name":"Diabetology and Growth Disorders Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."},{"name":"Department of Systems Medicine, University of Rome \u201cTor Vergata,\u201d Rome, Italy."},{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Iafusco","sequence":"additional","affiliation":[{"name":"Regional Center for Pediatric Diabetes, Department of Pediatrics, University of Campania Luigi Vanvitelli, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-980X","authenticated-orcid":true,"given":"Fabrizio","family":"Barbetti","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris A.","family":"Stoffers","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/17446651.2022.2035216"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-106"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1284"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030046"},{"issue":"5","key":"B5","doi-asserted-by":"crossref","first-page":"e197","DOI":"10.1111\/dme.12122","article-title":"Biallelic PDX1 (insulin promoter factor 1) mutations causing neonatal diabetes without exocrine pancreatic insufficiency","volume":"30","author":"De Franco","year":"2013","journal-title":"Diabet Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.06.083"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2024-004439"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2022.102561"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01502-7"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22584"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37028"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.040"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00260.2017"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.3.983"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34251"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.01.011"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200432"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1242\/dev.204379"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgae001"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-022-01972-2"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0721"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.04.007"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111857200"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0349"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/189343\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:39:38Z","timestamp":1779125978000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/189343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6,9]]},"published-print":{"date-parts":[[2025,6,9]]}},"alternative-id":["10.1172\/jci.insight.189343"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.189343","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"article-number":"e189343"}}