{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:14:22Z","timestamp":1773332062485,"version":"3.50.1"},"reference-count":24,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"unspecified","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["19\/005971"],"award-info":[{"award-number":["19\/005971"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute for Health Research (NIHR) Exeter Biomedical Research Centre, Exeter, UK","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["219606\/Z\/19\/Z"],"award-info":[{"award-number":["219606\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223187\/Z\/21\/Z"],"award-info":[{"award-number":["223187\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224600\/Z\/21\/Z"],"award-info":[{"award-number":["224600\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research England\u2019s Expanding Excellence in England","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2024,10,22]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Biallelic <jats:italic>PDX1<\/jats:italic> variants are a rare cause of isolated pancreatic agenesis and neonatal diabetes (NDM) without exocrine pancreatic insufficiency, with 17 cases reported in the literature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Research design and methods<\/jats:title>\n                  <jats:p>To determine the phenotypic variability caused by this rare genetic aetiology, we investigated 19 individuals with NDM resulting from biallelic disease-causing <jats:italic>PDX1<\/jats:italic> variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 19 individuals, 8 (42%) were confirmed to have exocrine insufficiency requiring replacement therapy. Twelve individuals (63.2%) had extrapancreatic features, including 8 (42%) with conditions affecting the duodenum and\/or hepatobiliary tract. Defects in duodenum development are consistent with previous <jats:italic>Pdx1<\/jats:italic> ablation studies in mice which showed abnormal rostral duodenum development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings show that recessive <jats:italic>PDX1<\/jats:italic> variants can cause a syndromic form of NDM, highlighting the need for clinical assessment of extrapancreatic features in individuals with NDM caused by <jats:italic>PDX1<\/jats:italic> variants.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjdrc-2024-004439","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T09:25:27Z","timestamp":1731576327000},"page":"e004439","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Widening the phenotypic spectrum caused by pathogenic <i>PDX1<\/i> variants in individuals with neonatal diabetes"],"prefix":"10.1136","volume":"12","author":[{"given":"Nicola","family":"Jeffery","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Al Nimri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayne A L","family":"Houghton","sequence":"additional","affiliation":[{"name":"Exeter Genomics Laboratory, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgenia","family":"Globa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"},{"name":"Ukrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew N","family":"Wakeling","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-473X","authenticated-orcid":false,"given":"Andrew T","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-8104","authenticated-orcid":false,"given":"Kashyap Amratlal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"},{"name":"Diabetes and Endocrinology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1437-7891","authenticated-orcid":false,"given":"Elisa","family":"De Franco","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"2025073111474627000_12.6.e004439.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60098-8"},{"key":"2025073111474627000_12.6.e004439.2","doi-asserted-by":"crossref","unstructured":"De Franco E , Johnson MB . Classification of neonatal diabetes. In: Rabbone I , Iafusco D , eds. Neonatal and Early Onset Diabetes Mellitus: From Pathogenesis to Novelty in Treatment. Cham: Springer International Publishing, 2023: 39\u201361.","DOI":"10.1007\/978-3-031-07008-2_4"},{"key":"2025073111474627000_12.6.e004439.3","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12122"},{"key":"2025073111474627000_12.6.e004439.4","doi-asserted-by":"crossref","DOI":"10.1111\/dme.15013","article-title":"Neonatal and early-onset diabetes in Ukraine: Atypical features and mortality","volume":"40","author":"Globa","year":"2023","journal-title":"Diabet Med"},{"key":"2025073111474627000_12.6.e004439.5","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1007\/s13312-017-1211-2","article-title":"PDX1 Gene Mutation with Permanent Neonatal Diabetes Mellitus with Annular Pancreas, Duodenal Atresia, Hypoplastic Gall Bladder and Exocrine Pancreatic Insufficiency","volume":"54","author":"Kulkarni","year":"2017","journal-title":"Indian Pediatr"},{"key":"2025073111474627000_12.6.e004439.6","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1284"},{"key":"2025073111474627000_12.6.e004439.7","doi-asserted-by":"crossref","DOI":"10.1186\/s13256-019-2149-x","article-title":"Iranian neonatal diabetes mellitus due to mutation in PDX1 gene: a case report","volume":"13","author":"Sahebi","year":"2019","journal-title":"J Med Case Rep"},{"key":"2025073111474627000_12.6.e004439.8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030046"},{"key":"2025073111474627000_12.6.e004439.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-106"},{"key":"2025073111474627000_12.6.e004439.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2009.00526.x"},{"key":"2025073111474627000_12.6.e004439.11","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4103\/ijem.ijem_429_21","article-title":"Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India","volume":"26","author":"Korula","year":"2022","journal-title":"Indian J Endocrinol Metab"},{"key":"2025073111474627000_12.6.e004439.12","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00592-022-01972-2","article-title":"Monogenic diabetes clinic (MDC): 3-year experience","volume":"60","author":"Rapini","year":"2023","journal-title":"Acta Diabetol"},{"key":"2025073111474627000_12.6.e004439.13","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2025073111474627000_12.6.e004439.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-2962-5"},{"key":"2025073111474627000_12.6.e004439.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.021"},{"key":"2025073111474627000_12.6.e004439.16","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1035"},{"key":"2025073111474627000_12.6.e004439.17","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.3.983"},{"key":"2025073111474627000_12.6.e004439.18","doi-asserted-by":"publisher","DOI":"10.1053\/J.GASTRO.2022.06.083"},{"key":"2025073111474627000_12.6.e004439.19","doi-asserted-by":"crossref","DOI":"10.1093\/pnasnexus\/pgae001","article-title":"Human RFX6 regulates endoderm patterning at the primitive gut tube stage","volume":"3","author":"Nakamura","year":"2024","journal-title":"PNAS Nexus"},{"key":"2025073111474627000_12.6.e004439.20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molmet.2018.01.011","article-title":"Genome-wide analysis of PDX1 target genes in human pancreatic progenitors","volume":"9","author":"Wang","year":"2018","journal-title":"Mol Metab"},{"key":"2025073111474627000_12.6.e004439.21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7449"},{"key":"2025073111474627000_12.6.e004439.22","doi-asserted-by":"publisher","DOI":"10.1038\/ng1097-138"},{"key":"2025073111474627000_12.6.e004439.23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2242"},{"key":"2025073111474627000_12.6.e004439.24","doi-asserted-by":"publisher","DOI":"10.1210\/me.14.12.1907"}],"container-title":["BMJ Open Diabetes Research &amp; Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjdrc-2024-004439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T18:47:53Z","timestamp":1753987673000},"score":1,"resource":{"primary":{"URL":"https:\/\/drc.bmj.com\/lookup\/doi\/10.1136\/bmjdrc-2024-004439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,11,14]]},"published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1136\/bmjdrc-2024-004439"],"URL":"https:\/\/doi.org\/10.1136\/bmjdrc-2024-004439","relation":{},"ISSN":["2052-4897"],"issn-type":[{"value":"2052-4897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]}}}