{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T04:18:01Z","timestamp":1777177081169,"version":"3.51.4"},"reference-count":21,"publisher":"BMJ","issue":"12","funder":[{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"crossref","award":["2019B-4"],"award-info":[{"award-number":["2019B-4"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20ek0109373h0003"],"award-info":[{"award-number":["20ek0109373h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,7,19]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Two imprinting control centres, <jats:italic>H19\/IGF2<\/jats:italic>:IG-differentialy methylated region (DMR) and <jats:italic>KCNQ1OT1<\/jats:italic>:TSS-DMR, reside on chromosome 11p15.5. Paternal deletions involving the <jats:italic>KCNQ1OT1<\/jats:italic>:TSS-DMR result in variable phenotypes, namely, normal phenotype, Silver-Russel syndrome (SRS) and fetal demise. However, expression analyses for <jats:italic>CDKN1C<\/jats:italic> in these patients are very limited.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Cases<\/jats:title>\n                  <jats:p>Patient 1 (adult woman) and patient 2 (boy in early childhood) showed prenatal and postnatal growth failure and clinical suspicion of SRS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Molecular analyses<\/jats:title>\n                  <jats:p>Both patients showed hypermethylation of the <jats:italic>KCNQ1OT1<\/jats:italic>:TSS-DMR caused by the paternal heterozygous de novo deletions involving the <jats:italic>KCNQ1OT1<\/jats:italic>:TSS-DMR, but not including <jats:italic>CDKN1C<\/jats:italic> enhancers. The deletion sizes were 5 kb and 12 kb for patients 1 and 2, respectively. <jats:italic>CDKN1C<\/jats:italic> gene expressions in immortalised leucocytes of both patients were increased compared with those of controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Paternal deletions involving the <jats:italic>KCNQ1OT1<\/jats:italic>:TSS-DMR, but not including <jats:italic>CDKN1C<\/jats:italic> enhancers, disrupt <jats:italic>KCNQ1OT1<\/jats:italic> expression, strongly activate <jats:italic>CDKN1C<\/jats:italic> expression and consequently cause severe growth failure.<\/jats:p>\n               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