{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:38:06Z","timestamp":1792057086486,"version":"4.4.0"},"reference-count":17,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2010,12,16]]},"published-print":{"date-parts":[[2011,5]]},"abstract":"\n Silver\u2013Russell syndrome (SRS) is characterised by prenatal and postnatal growth retardation, dysmorphic facial features, and body asymmetry. In 35\u201360% of SRS cases the paternally methylated imprinting control region (ICR) upstream of the\n H19<\/jats:italic>\n gene (H19-ICR) is hypomethylated, leading to downregulation of\n IGF2<\/jats:italic>\n and bi-allelic expression of\n H19<\/jats:italic>\n .\n H19<\/jats:italic>\n and\n IGF2<\/jats:italic>\n are reciprocally imprinted genes on chromosome 11p15. The expression is regulated by the imprinted methylation of the ICR, which modulates the transcription of\n H19<\/jats:italic>\n and\n IGF2<\/jats:italic>\n facilitated by enhancers downstream of\n H19<\/jats:italic>\n . A promoter element of\n IGF2<\/jats:italic>\n , IGF2P0, is differentially methylated equivalently to the H19-ICR, though in a small number of SRS cases this association is disrupted\u2014that is, hypomethylation affects either H19-ICR or IGF2P0.\n <\/jats:p>\n \n Three pedigrees associated with hypomethylation of IGF2P0 in the probands are presented here, two with paternally derived deletions, and one with a balanced translocation of inferred paternal origin. They all have a breakpoint within the\n H19<\/jats:italic>\n \/\n IGF2<\/jats:italic>\n enhancer region. One proband has severe growth retardation, the others have SRS.\n <\/jats:p>\n \n This is the first report of paternally derived structural chromosomal mutations in 11p15 causing SRS. These cases define a novel aetiology of the growth retardation in SRS, namely, dissociation of\n IGF2<\/jats:italic>\n from its enhancers.\n <\/jats:p>","DOI":"10.1136\/jmg.2010.086504","type":"journal-article","created":{"date-parts":[[2011,1,29]],"date-time":"2011-01-29T20:25:39Z","timestamp":1296332739000},"page":"308-311","source":"Crossref","is-referenced-by-count":38,"title":["Deletions and rearrangements of the\n H19<\/i>\n \/\n IGF2<\/i>\n enhancer region in patients with Silver\u2013Russell syndrome and growth retardation"],"prefix":"10.1136","volume":"48","author":[{"given":"Karen","family":"Gr\u00f8nskov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L","family":"Poole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne M 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Karen","family":"Temple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne E","family":"Boonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J G","family":"Mackay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2011,1,28]]},"reference":[{"key":"2025100511280106000_48.5.308.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053017"},{"key":"2025100511280106000_48.5.308.2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.038687"},{"key":"2025100511280106000_48.5.308.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1629"},{"key":"2025100511280106000_48.5.308.4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0354"},{"key":"2025100511280106000_48.5.308.5","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.057059"},{"key":"2025100511280106000_48.5.308.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028936"},{"key":"2025100511280106000_48.5.308.7","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1002\/ajmg.a.33398","article-title":"Chromosome 11p15 duplication in Silver-Russell syndrome due 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