{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:53:09Z","timestamp":1780109589492,"version":"3.54.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01-DK056268"],"award-info":[{"award-number":["R01-DK056268"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01-DK098517"],"award-info":[{"award-number":["R01-DK098517"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006458","name":"CHOP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001878"],"award-info":[{"award-number":["UL1TR001878"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Some children with diazoxide-unresponsive congenital hyperinsulinism (HI) lack any detectable disease-causing mutation in peripheral-blood DNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This work aimed to examine whether somatic postzygotic mutations of known HI genes are responsible for disease in children with diazoxide-unresponsive HI requiring surgery with histology not classified as focal or localized islet nuclear enlargement (LINE), and without detectable mutations by standard genetic testing of peripheral blood DNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Next-generation sequencing (NGS) was performed on specimens of pancreas from 10 children with diazoxide-unresponsive HI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Four unique GCK mutations were identified at low levels of mosaicism ranging from 4.4% to 10.1% in pancreatic DNA from 5 of these 10 children. The GCK mutations were not detectable in peripheral-blood DNA by NGS in 3 cases from which peripheral-blood DNA was available for testing. All 4 GCK mutations have been previously published as activating HI mutations. The histology was consistent with diffuse HI in 4 of the 5 cases with mosaic GCK mutations. In one of these, hypomethylation of IC2 on chromosome 11p was identified in pancreatic and peripheral-blood DNA. Histology of the fifth case revealed minor islet abnormalities suggestive of Beckwith-Wiedemann spectrum although molecular analysis for 11pUPD was negative in pancreas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results indicate that postzygotic somatic GCK mutations are responsible for some cases of nonfocal diazoxide-unresponsive HI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae713","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T19:22:23Z","timestamp":1728415343000},"page":"1923-1928","source":"Crossref","is-referenced-by-count":6,"title":["Low-Level Mosaic <i>GCK<\/i> Mutations in Children With Diazoxide-Unresponsive Congenital Hyperinsulinism"],"prefix":"10.1210","volume":"110","author":[{"given":"Kara E","family":"Boodhansingh","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Lord","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N Scott","family":"Adzick","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Bhatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arupa","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Stanley","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-8087","authenticated-orcid":false,"given":"Diva D","family":"De Leon","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"issue":"2","key":"2025062418111140300_dgae713-B1","doi-asserted-by":"crossref","first-page":"E355","DOI":"10.1210\/jc.2012-2169","article-title":"Genotype and phenotype correlations in 417 children with congenital hyperinsulinism","volume":"98","author":"Snider","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025062418111140300_dgae713-B2","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1172\/JCI119594","article-title":"Somatic deletion of the imprinted 11p15 region in sporadic persistent 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