{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:56:06Z","timestamp":1775760966981,"version":"3.50.1"},"reference-count":35,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T00:00:00Z","timestamp":1569196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18ek0109301"],"award-info":[{"award-number":["JP18ek0109301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18ek0109297"],"award-info":[{"award-number":["JP18ek0109297"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18ek0109266"],"award-info":[{"award-number":["18ek0109266"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0109373"],"award-info":[{"award-number":["JP19ek0109373"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17H06428"],"award-info":[{"award-number":["JP17H06428"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>IGF2 is a paternally expressed growth-promoting gene. Here, we report five cases with IGF2 mutations and review IGF2 mutation-positive patients described in the literature. We also compare clinical features between patients with IGF2 mutations and those with H19\/IGF2:IG-DMR epimutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We recruited five cases with IGF2 mutations: case 1 with a splice site mutation (c.\u20136\u20131G&amp;gt;C) leading to skipping of exon 2 and cases 2\u20135 with different missense mutations (p.(Cys70Tyr), p.(Cys71Arg), p.(Cys33Ser), and p.(Cys45Ser)) affecting cysteine residues involved in the S-S bindings. All the mutations resided on the paternally inherited allele, and the mutation of case 5 was present in a mosaic condition. Clinical assessment revealed Silver\u2013Russell syndrome (SRS) phenotype with Netchine\u2013Harbison scores of \u22655\/6 in all the apparently nonmosaic 14 patients with IGF2 mutations (cases 1\u20134 described in this study and 10 patients reported in the literature). Furthermore, compared with H19\/IGF2:IG-DMR epimutations, IGF2 mutations were associated with low frequency of hemihypoplasia, high frequency of feeding difficulty and\/or reduced body mass index, and mild degree of relative macrocephaly, together with occasional development of severe limb malformations, high frequency of cardiovascular anomalies and developmental delay, and low serum IGF-II values.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study indicates that IGF2 mutations constitute a rare but important cause of SRS. Furthermore, while both IGF2 mutations and H19\/IGF2:IG-DMR epimutations lead to SRS, a certain degree of phenotypic difference is observed between the two groups, probably due to the different IGF2 expression pattern in target tissues.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz034","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T11:31:37Z","timestamp":1569238297000},"page":"116-125","source":"Crossref","is-referenced-by-count":34,"title":["<i>IGF2<\/i> Mutations"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-8640","authenticated-orcid":false,"given":"Yohei","family":"Masunaga","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanobu","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6001-6395","authenticated-orcid":false,"given":"Kaori","family":"Yamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-4214","authenticated-orcid":false,"given":"Yasuko","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-1545","authenticated-orcid":false,"given":"Yuki","family":"Kawashima-Sonoyama","sequence":"additional","affiliation":[{"name":"Division of Pediatrics and Perinatology, Faculty of Medicine Tottori University, Yonago, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9676-865X","authenticated-orcid":false,"given":"Naoya","family":"Morisada","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Hyogo Prefectural Kobe Children\u2019s Hospital, Kobe, Japan"},{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-8174","authenticated-orcid":false,"given":"Kazumoto","family":"Iijima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhisa","family":"Ohata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3803-4500","authenticated-orcid":false,"given":"Noriyuki","family":"Namba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan"},{"name":"Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Suzumura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dokkyo Medical University, Mibu, 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