{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:07:33Z","timestamp":1791587253583,"version":"4.3.4"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Barts Charity Large Project Grant","award":["MRC0161"],"award-info":[{"award-number":["MRC0161"]}]},{"name":"European Society for Paediatric Endocrinology (ESPE) Research Fellowship and Barts Charity Clinical Research Fellowship","award":["MGU0519"],"award-info":[{"award-number":["MGU0519"]}]},{"name":"NIHR Advanced fellowship","award":["NIHR300098"],"award-info":[{"award-number":["NIHR300098"]}]},{"name":"Natural Sciences and Engineering Council of Canada","award":["RGPIN\/5485-2017"],"award-info":[{"award-number":["RGPIN\/5485-2017"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN: 342178-2008"],"award-info":[{"award-number":["RGPIN: 342178-2008"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>\n                    Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation.\n                    <jats:italic>HMGA2<\/jats:italic>\n                    variants are a rare cause of SRS and its functional role in human linear growth is unclear. Patients with suspected SRS negative for 11p15LOM\/mUPD7 underwent whole-exome and\/or targeted-genome sequencing. Mutant HMGA2 protein expression and nuclear localization were assessed. Two\n                    <jats:italic>Hmga2<\/jats:italic>\n                    -knockin mouse models were generated. Five clinical SRS patients harbored\n                    <jats:italic>HMGA2<\/jats:italic>\n                    variants with differing functional impacts: 2 stop-gain nonsense variants (c.49G&gt;T, c.52C&gt;T), c.166A&gt;G missense variant, and 2 frameshift variants (c.144delC, c.145delA) leading to an identical, extended-length protein. Phenotypic features were highly variable. Nuclear localization was reduced\/absent for all variants except c.166A&gt;G. Homozygous knockin mice recapitulating the c.166A&gt;G variant (\n                    <jats:italic>Hmga2<\/jats:italic>\n                    <jats:sup>K56E<\/jats:sup>\n                    ) exhibited a growth-restricted phenotype. An\n                    <jats:italic>\n                      Hmga2\n                      <jats:sup>Ter76<\/jats:sup>\n                    <\/jats:italic>\n                    -knockin mouse model lacked detectable full-length Hmga2 protein, similarly to patient 3 and 5 variants. These mice were infertile, with a pygmy phenotype. We report a heterogeneous group of individuals with SRS harboring variants in\n                    <jats:italic>HMGA2<\/jats:italic>\n                    and describe the first\n                    <jats:italic>Hmga2<\/jats:italic>\n                    missense knockin mouse model (\n                    <jats:italic>Hmga2<\/jats:italic>\n                    <jats:sup>K56E<\/jats:sup>\n                    ) to our knowledge causing a growth-restricted phenotype. In patients with clinical features of SRS but negative genetic screening,\n                    <jats:italic>HMGA2<\/jats:italic>\n                    should be included in next-generation sequencing testing approaches.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.169425","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:26:26Z","timestamp":1712305586000},"source":"Crossref","is-referenced-by-count":10,"title":["Characterization of HMGA2 variants expands the spectrum of Silver-Russell syndrome"],"prefix":"10.1172","volume":"9","author":[{"given":"Avinaash V.","family":"Maharaj","sequence":"first","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, QMUL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-6547","authenticated-orcid":true,"given":"Emily","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, QMUL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thatchawan","family":"Thanasupawat","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd D.","family":"Joustra","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Triggs-Raine","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-7517","authenticated-orcid":true,"given":"Masanobu","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina G.","family":"Kant","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"van der Kaay","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Paediatrics, Erasmus University Medical Centre, Sophia Children\u2019s Hospital, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Clement-de Boers","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Juliana Children\u2019s Hospital\/Haga Teaching Hospital, The Hague, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice S.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-2661","authenticated-orcid":true,"given":"Gabriel Amador","family":"Aguirre","sequence":"additional","affiliation":[{"name":"CITES - Escuela Nacional de Medicina, TEC de Monterrey, Monterrey, Nuevo Le\u00f3n, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Mart\u00edn del Estal","sequence":"additional","affiliation":[{"name":"CITES - Escuela Nacional de Medicina, TEC de Monterrey, Monterrey, Nuevo Le\u00f3n, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Inmaculada","family":"Castilla de Cort\u00e1zar Larrea","sequence":"additional","affiliation":[{"name":"CITES - Escuela Nacional de Medicina, TEC de Monterrey, Monterrey, Nuevo Le\u00f3n, Mexico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Massoud","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, HCA Healthcare UK, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermine A.","family":"van Duyvenvoorde","sequence":"additional","affiliation":[{"name":"Laboratory for Diagnostic Genome analysis (LDGA), Department of Clinical Genetics, Leiden University Medical Centre, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan","family":"De Bruin","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology, Department of Paediatrics, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-9049","authenticated-orcid":true,"given":"Vivian","family":"Hwa","sequence":"additional","affiliation":[{"name":"Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Klonisch","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada."},{"name":"Department of Pathology, and"},{"name":"Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Hombach-Klonisch","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada."},{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-1931","authenticated-orcid":true,"given":"Helen L.","family":"Storr","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, QMUL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.138"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102979"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-020-00865-x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng2121"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.04.027"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.225"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.215"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.03.001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa273"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.29"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2012.794"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137999"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2271"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2009.11.007"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.052"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-436"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/genes12020269"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.04.024"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402180"},{"issue":"10","key":"B20","first-page":"3036","article-title":"HMGA2 gene silencing reduces epithelial-mesenchymal transition and lymph node metastasis in cervical cancer through inhibiting the ATR\/Chk1 signaling pathway","volume":"10","author":"Wang","year":"2018","journal-title":"Am J Transl Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-022-09537-w"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2180"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2550"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-015-0462-8"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2020.1736559"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6938"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215696"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124504"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.01.014"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1593\/neo.121988"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/genes12020269"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00037"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13228"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2021.1924948"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12390"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201700388"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nature09410"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/ng.121"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/ng.125"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.105"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02288"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300032511"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/376771a0"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20146759"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/89.4.295"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039929"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140749"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/age.13016"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.116.196667"},{"key":"B50","doi-asserted-by":"crossref","unstructured":"Kuwayama N, et al. A simple method for gene expression in endo- and ectodermal cells in mouse embryos before neural tube closure preprint. https:\/\/doi.org\/10.1101\/2020.05.14.086330 Posted on bioRxiv March 4, 2023","DOI":"10.1101\/2020.05.14.086330"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkab417"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2015.06.005"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.10.1583"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22888"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx759"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000646"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl1106"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200800193"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2009.09.004"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07270.x"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.03.015"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/74207"},{"issue":"19","key":"B63","first-page":"4793","article-title":"The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis","volume":"59","author":"Battista","year":"1999","journal-title":"Cancer Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3388"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.atg.2015.08.002"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz322"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.07.017"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.908"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/169425\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:40:28Z","timestamp":1779140428000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/169425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":74,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,2,15]]},"published-print":{"date-parts":[[2024,3,22]]}},"alternative-id":["10.1172\/jci.insight.169425"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.169425","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]},"article-number":"e169425"}}