{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T23:15:42Z","timestamp":1773443742319,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 CA193915"],"award-info":[{"award-number":["K08 CA193915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the <jats:italic>NSD1<\/jats:italic> gene. Genotype\u2013phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in <jats:italic>NSD1<\/jats:italic>. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic <jats:italic>NSD1<\/jats:italic> mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by <jats:italic>NSD1<\/jats:italic> gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by <jats:italic>NSD1<\/jats:italic> mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that <jats:italic>NSD1<\/jats:italic> haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature.<\/jats:p>","DOI":"10.1002\/ajmg.a.61062","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T10:45:02Z","timestamp":1549363502000},"page":"542-551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Hyperinsulinemic hypoglycemia in seven patients with de novo <i>NSD1<\/i> mutations"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-2913","authenticated-orcid":false,"given":"Katheryn","family":"Grand","sequence":"first","affiliation":[{"name":"Division of Human Genetics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Gonzalez\u2010Gandolfi","sequence":"additional","affiliation":[{"name":"Division of Human Genetics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-9790","authenticated-orcid":false,"given":"Amanda M.","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes The Children's Hospital of Philadelphia  Philadelphia Pennsylvania"},{"name":"Department of Pediatrics Perelman School of Medicine, The University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0343-6083","authenticated-orcid":false,"given":"Deema","family":"Aljeaid","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"Department of Genetic Medicine, Faculty of Medicine King Abdulaziz University  Jeddah Saudi 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