{"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":1780109589666,"version":"3.54.0"},"reference-count":48,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> The hyperinsulinemia-hyperammonemia syndrome (HIHA) is the second most common cause of congenital hyperinsulinism and is caused by activating heterozygous missense mutations in <i>GLUD1<\/i>. In the majority of HIHA cases, the <i>GLUD1<\/i> mutation is found to be de novo. We have identified 3 patients in whom clinical evaluation was suggestive of HIHA but with negative mutation analysis in peripheral blood DNA for <i>GLUD1<\/i> as well as other known HI genes. <b><i>Methods:<\/i><\/b> We performed next-generation sequencing (NGS) on peripheral blood DNA from two children with clinical features of HIHA in order to look for mosaic mutations in <i>GLUD1<\/i>. Pancreas tissue was also available in one of these cases for NGS. In addition, NGS was performed on peripheral blood DNA from a woman with a history of HI in infancy whose child had HIHA due to a presumed de novo <i>GLUD1<\/i> mutation. <b><i>Results:<\/i><\/b> Mosaic <i>GLUD1<\/i> mutations were identified in these 3 cases at percent mosaicism ranging from 2.7% to 10.4% in peripheral blood. In one case with pancreas tissue available, the mosaic <i>GLUD1<\/i> mutation was present at 17.9% and 28.9% in different sections of the pancreas. Two unique GLUD1 mutations were identified in these cases, both of which have been previously reported (c.1493c&#x3e;t\/p.Ser445Leu and c.820c&#x3e;t\/p.Arg221Cys). <b><i>Conclusion:<\/i><\/b> The results suggest that low-level mosaic mutations in known HI genes may be the underlying molecular mechanism in some children with HI who have negative genetic testing in peripheral blood DNA. <\/jats:p>","DOI":"10.1159\/000526203","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:00:34Z","timestamp":1660251634000},"page":"492-498","source":"Crossref","is-referenced-by-count":11,"title":["Mosaic <b><i>GLUD1<\/i><\/b> Mutations Associated with Hyperinsulinism Hyperammonemia Syndrome"],"prefix":"10.1159","volume":"95","author":[{"given":"Kara E.","family":"Boodhansingh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1959-4457","authenticated-orcid":false,"given":"Elizabeth","family":"Rosenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Scott","family":"Adzick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Bhatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arupa","family":"Ganguly","sequence":"additional","affiliation":[],"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":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4881-9392","authenticated-orcid":false,"given":"Charles A.","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref1"},{"key":"ref2"},{"key":"ref3"},{"key":"ref4"},{"key":"ref5"},{"key":"ref6"},{"key":"ref7"},{"key":"ref8"},{"key":"ref9"},{"key":"ref10"},{"key":"ref11"},{"key":"ref12"},{"key":"ref13"},{"key":"ref14"},{"key":"ref15"},{"key":"ref16"},{"key":"ref17"},{"key":"ref18"},{"key":"ref19"},{"key":"ref20"},{"key":"ref21"},{"key":"ref22"},{"key":"ref23"},{"key":"ref24"},{"key":"ref25"},{"key":"ref26"},{"key":"ref27"},{"key":"ref28"},{"key":"ref29"},{"key":"ref30"},{"key":"ref31"},{"key":"ref32"},{"key":"ref33"},{"key":"ref34"},{"key":"ref35"},{"key":"ref36"},{"key":"ref37"},{"key":"ref38"},{"key":"ref39"},{"key":"ref40"},{"key":"ref41"},{"key":"ref42"},{"key":"ref43"},{"key":"ref44"},{"key":"ref45"},{"key":"ref46"},{"key":"ref47"},{"key":"ref48"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/526203","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/526203","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:13:29Z","timestamp":1745421209000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000526203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,11,11]]},"published-print":{"date-parts":[[2022,11,17]]}},"URL":"https:\/\/doi.org\/10.1159\/000526203","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.20472129","asserted-by":"subject"}]},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}