{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:15:19Z","timestamp":1790680519961,"version":"4.1.0"},"reference-count":10,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T00:00:00Z","timestamp":1362009600000},"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":["Diabet. Med."],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Recessive <jats:italic>PDX1<\/jats:italic> (<jats:italic>IPF1<\/jats:italic>) mutations are a rare cause of pancreatic agenesis, with three cases reported worldwide. A recent report described two cousins with a homozygous hypomorphic <jats:italic>PDX1<\/jats:italic> mutation causing permanent neonatal diabetes with subclinical exocrine insufficiency. The aim of our study was to investigate the possibility of hypomorphic <jats:italic>PDX1<\/jats:italic> mutations in a large cohort of patients with permanent neonatal diabetes and no reported pancreatic hypoplasia or exocrine insufficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>PDX1<\/jats:italic> was sequenced in 103 probands with isolated permanent neonatal diabetes in whom <jats:italic>ABCC8<\/jats:italic>,<jats:italic> KCNJ11<\/jats:italic> and <jats:italic>INS<\/jats:italic> mutations had been excluded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequencing analysis identified biallelic <jats:italic>PDX1<\/jats:italic> mutations in three of the 103 probands with permanent neonatal diabetes (2.9%). One proband and his affected brother were compound heterozygotes for a frameshift and a novel missense mutation (p.A34fsX191; c.98dupC and p.P87L; c.260C&gt;T). The other two probands were homozygous for novel <jats:italic>PDX1<\/jats:italic> missense mutations (p.A152G; c.455C&gt;G and p.R176Q; c.527G&gt;A). Both mutations affect highly conserved residues located within the homeobox domain. None of the four cases showed any evidence of exocrine pancreatic insufficiency, either clinically, or, where data were available, biochemically. In addition a heterozygous nonsense mutation (p.C18X; c.54C&gt;A) was identified in a fourth case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that recessive <jats:italic>PDX1<\/jats:italic> mutations are a rare but important cause of isolated permanent neonatal diabetes in patients without pancreatic hypoplasia\/agenesis. Inclusion of the <jats:italic>PDX1<\/jats:italic> gene in mutation screening for permanent neonatal diabetes is recommended as a genetic diagnosis reveals the mode of inheritance, allows accurate estimation of recurrence risks and confirms the requirement for insulin treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12122","type":"journal-article","created":{"date-parts":[[2013,1,16]],"date-time":"2013-01-16T10:55:00Z","timestamp":1358333700000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Biallelic <i>PDX1<\/i> (insulin promoter factor\u00a01) mutations causing neonatal diabetes without exocrine pancreatic insufficiency"],"prefix":"10.1111","volume":"30","author":[{"given":"E.","family":"De Franco","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Shaw\u2010Smith","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. L.","family":"Edghill","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder\u2010 und Jugendmedizin St Vincenz\u2010Krankenhaus Paderborn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Otte","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder\u2010 und Jugendmedizin St Vincenz\u2010Krankenhaus Paderborn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Ebinger","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder\u2010 und Jugendmedizin St Vincenz\u2010Krankenhaus Paderborn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Varthakavi","sequence":"additional","affiliation":[{"name":"TNM College and BYL Nair Charitable Hospital Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Vasanthi","sequence":"additional","affiliation":[{"name":"Kanchi Kamakoti CHILDS Trust Hospital and Childs Trust Medical Research Foundation (CTMRF) Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Edvardsson","sequence":"additional","affiliation":[{"name":"Centrallasarettet Vaxjo Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. T.","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ellard","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1416-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-010-9149-x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1475"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030046"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-106"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2009.00526.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1035"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112029"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1284"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2011.03269.x"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12122","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:25:15Z","timestamp":1695572715000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.12122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,28]]},"references-count":10,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1111\/dme.12122"],"URL":"https:\/\/doi.org\/10.1111\/dme.12122","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,28]]},"assertion":[{"value":"2013-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}