{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:45:53Z","timestamp":1778154353717,"version":"3.51.4"},"reference-count":36,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:p>OBJECTIVE. Permanent neonatal diabetes mellitus caused by developmental failure of the pancreas is rare. Thus far, only a few genetic causes have been reported. We now report the clinical and genetic aspects of 4 more cases of permanent neonatal diabetes mellitus caused by pancreatic agenesis or hypoplasia.<\/jats:p><jats:p>PATIENTS AND METHODS. All 4 of the patients were from consanguineous kinships, and all presented with diabetes mellitus and pancreatic exocrine insufficiency. Three patients had pancreatic agenesis, and 1 had pancreatic hypoplasia on computed tomography scan. DNA was extracted from blood samples of patients and unaffected family members. Specific genes were amplified by polymerase chain reaction and characterized by DNA sequencing.<\/jats:p><jats:p>RESULTS. Several genes that encode transcription factors that have known roles in pancreas development were characterized in the affected children and unaffected family members. These genes include Pdx1, the master regulator of pancreas development and \u03b2-cell differentiation, and other transcription factors that are expressed early in pancreas development, namely, Ptf1a, Sox9, Sox17, Hnf6, and HlxB9. Several novel polymorphisms were found in our patients. However, these were also present in unaffected individuals. No disease-causing mutations were found in any of these genes.<\/jats:p><jats:p>CONCLUSIONS. These findings add to the 4 cases already in the literature in which the Pdx1 structural gene has been found to be normal in patients with pancreatic agenesis or hypoplasia. The analysis here has been extended to include the screening of 4 other candidate genes in addition to promoter elements upstream of the Pdx1. Two of the cases occurred in a sibling pair, and 2 were isolated, so there may be more than 1 etiology in the cases reported here.<\/jats:p>","DOI":"10.1542\/peds.2007-3543","type":"journal-article","created":{"date-parts":[[2008,6,2]],"date-time":"2008-06-02T14:15:50Z","timestamp":1212416150000},"page":"e1541-e1547","source":"Crossref","is-referenced-by-count":26,"title":["Neonatal and Late-Onset Diabetes Mellitus Caused by Failure of Pancreatic Development: Report of 4 More Cases and a Review of the Literature"],"prefix":"10.1542","volume":"121","author":[{"given":"Rongrong","family":"Chen","sequence":"first","affiliation":[{"name":"Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, King's College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Hussain","sequence":"additional","affiliation":[{"name":"London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom"},{"name":"Institute of Child Health, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Al-Ali","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology, Hamad Hospital, Doha, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehul T.","family":"Dattani","sequence":"additional","affiliation":[{"name":"London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom"},{"name":"Institute of Child Health, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hindmarsh","sequence":"additional","affiliation":[{"name":"London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom"},{"name":"Institute of Child Health, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, King's College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phil","family":"Marsh","sequence":"additional","affiliation":[{"name":"Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, King's College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2008,6,1]]},"reference":[{"key":"2021120905433442000_R1","doi-asserted-by":"crossref","unstructured":"Temple IK, Gardner RJ, Mackay DJ, Barber JC, Robinson DO, Shield JP. 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