{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:28:14Z","timestamp":1790173694621,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"1","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Disorders","doi-asserted-by":"crossref","award":["R01DK083762"],"award-info":[{"award-number":["R01DK083762"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Disorders","doi-asserted-by":"crossref","award":["DK41301"],"award-info":[{"award-number":["DK41301"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"crossref","award":["RT2-01985"],"award-info":[{"award-number":["RT2-01985"]}],"id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,16]]},"abstract":"<jats:p>\n                    Biallelic mutations of the gene encoding the transcription factor NEUROG3 are associated with a rare disorder that presents in neonates as generalized malabsorption \u2014 due to a complete absence of enteroendocrine cells \u2014 followed, in early childhood or beyond, by insulin-dependent diabetes mellitus (IDDM). The commonly delayed onset of IDDM suggests a differential requirement for NEUROG3 in endocrine cell generation in the human pancreas versus the intestine. However, previously identified human mutations were hypomorphic and, hence, may have had residual function in pancreas. We report 2 patients with biallelic functionally null variants of the\n                    <jats:italic>NEUROG3<\/jats:italic>\n                    gene who nonetheless did not present with IDDM during infancy but instead developed permanent IDDM during middle childhood ages. The variants showed no evidence of function in traditional promoter-based assays of NEUROG3 function and also failed to exhibit function in a variety of potentially novel in vitro and in vivo molecular assays designed to discern residual NEUROG3 function. These findings imply that, unlike in mice, pancreatic endocrine cell generation in humans is not entirely dependent on\n                    <jats:italic>NEUROG3<\/jats:italic>\n                    expression and, hence, suggest the presence of unidentified redundant in vivo pathways in human pancreas capable of yielding \u03b2 cell mass sufficient to maintain euglycemia until early childhood.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127657","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T12:18:19Z","timestamp":1575548299000},"source":"Crossref","is-referenced-by-count":20,"title":["Null mutations of NEUROG3 are associated with delayed-onset diabetes mellitus"],"prefix":"10.1172","volume":"5","author":[{"given":"R. Sergio","family":"Solorzano-Vargas","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Department of Pediatrics, Mattel Children\u2019s Hospital and David Geffen School of Medicine at UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-885X","authenticated-orcid":true,"given":"Matthew","family":"Bjerknes","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Department of Pediatrics, Mattel Children\u2019s Hospital and David Geffen School of Medicine at UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Vincent","family":"Wu","sequence":"additional","affiliation":[{"name":"Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA."},{"name":"Department of Medicine, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel G.","family":"Garcia-Careaga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pisit","family":"Pitukcheewanont","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, Children\u2019s Hospital Los Angeles and University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, 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