{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:06:42Z","timestamp":1784074002345,"version":"3.55.0"},"reference-count":18,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK056268"],"award-info":[{"award-number":["R01-DK056268"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK098517"],"award-info":[{"award-number":["R01-DK098517"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR001878"],"award-info":[{"award-number":["UL1TR001878"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Noncoding variants in hexokinase 1 (HK1) were first associated with congenital hyperinsulinism (HI) in a large family with diazoxide-responsive HI in 2008. Since then, additional cases have been reported in the literature with noncoding variants in HK1 associated with variable HI phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We sequenced a 350 bp region in intron 2 of HK1 in 281 individuals with genetics-negative HI to identify additional cases related to non-coding HK1 variants and to characterize the clinical features of these cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 16 unique non-coding variants in intron 2 of HK1 in 18 individuals with genetics-negative HI (18\/281, 6.4%). In 7 cases (7\/18, 39%), the HK1 variant was inherited from a parent (2 maternal, 5 paternal); 2 are known to be affected with HI. In 9 cases, the HK1 variant was de novo (9\/18, 50%). The age of presentation of HI ranged from day of life 1 to 21 months of age. Seven cases had diazoxide-responsive HI (7\/18, 39%). Eleven cases were diazoxide unresponsive (11\/18, 61%); 5 underwent pancreatectomy at ages ranging from 6 months to 3 years of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Noncoding variants in intron 2 of the HK1 gene have now been associated with HI in a growing number of cases. Our findings suggest that a significant proportion of individuals with negative genetics in genes currently known to be associated with HI may harbor HK1 intron 2 variants. Identifying these cases is important for clinical care as well as for assessing recurrence risk for families.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag108","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T12:46:44Z","timestamp":1772887604000},"page":"2242-2250","source":"Crossref","is-referenced-by-count":0,"title":["Noncoding Variants in Intron 2 of\n                    <i>HK1<\/i>\n                    Associated With Hyperinsulinism With Variable Clinical Phenotype"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-1372","authenticated-orcid":false,"given":"Kara E","family":"Boodhansingh","sequence":"first","affiliation":[{"name":"Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia , Philadelphia, PA 19104 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E","family":"Benjet","sequence":"additional","affiliation":[{"name":"Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Chen","sequence":"additional","affiliation":[{"name":"Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-1407","authenticated-orcid":false,"given":"Christine A","family":"Juliana","sequence":"additional","affiliation":[{"name":"Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia , Philadelphia, PA 19104 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