{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:16:02Z","timestamp":1791414962539,"version":"4.3.3"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,7,6]]},"abstract":"<jats:p>\n                    Loss of imprinting at\n                    <jats:italic>IGF2<\/jats:italic>\n                    , generally through an\n                    <jats:italic>H19<\/jats:italic>\n                    -independent mechanism, is associated with a large percentage of patients with the overgrowth and cancer predisposition condition Beckwith\u2013Wiedemann syndrome (BWS). Imprinting control elements are proposed to exist within the\n                    <jats:italic>KvLQT1<\/jats:italic>\n                    locus, because multiple BWS-associated chromosome rearrangements disrupt this gene. We have identified an evolutionarily conserved, maternally methylated CpG island (\n                    <jats:italic>KvDMR1<\/jats:italic>\n                    ) in an intron of the\n                    <jats:italic>KvLQT1<\/jats:italic>\n                    gene. Among 12 cases of BWS with normal\n                    <jats:italic>H19<\/jats:italic>\n                    methylation, 5 showed demethylation of\n                    <jats:italic>KvDMR1<\/jats:italic>\n                    in fibroblast or lymphocyte DNA; whereas, in 4 cases of BWS with\n                    <jats:italic>H19<\/jats:italic>\n                    hypermethylation, methylation at\n                    <jats:italic>KvDMRl<\/jats:italic>\n                    was normal. Thus, inactivation of\n                    <jats:italic>H19<\/jats:italic>\n                    and hypomethylation at\n                    <jats:italic>KvDMR1<\/jats:italic>\n                    (or an associated phenomenon) represent distinct epigenetic anomalies associated with biallelic expression of\n                    <jats:italic>IGF2<\/jats:italic>\n                    . Reverse transcription\u2013PCR analysis of the human and syntenic mouse loci identified the presence of a\n                    <jats:italic>KvDMR1<\/jats:italic>\n                    -associated RNA transcribed exclusively from the paternal allele and in the opposite orientation with respect to the maternally expressed\n                    <jats:italic>KvLQT1<\/jats:italic>\n                    gene. We propose that\n                    <jats:italic>KvDMR1<\/jats:italic>\n                    and\/or its associated antisense RNA (\n                    <jats:italic>KvLQT1-AS<\/jats:italic>\n                    ) represents an additional imprinting control element or center in the human 11p15.5 and mouse distal 7 imprinted domains.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.14.8064","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"8064-8069","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":325,"title":["A maternally methylated CpG island in\n                    <i>KvLQT1<\/i>\n                    is associated with an antisense paternal transcript and loss of imprinting in Beckwith\u2013Wiedemann syndrome"],"prefix":"10.1073","volume":"96","author":[{"given":"Nancy J.","family":"Smilinich","sequence":"first","affiliation":[{"name":"Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263; Division of Genetics, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, United Kingdom; Laboratory of Stem Cell Biology, Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen D.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263; Division of Genetics, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, United Kingdom; Laboratory of Stem Cell Biology, Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina V.","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263; Division of Genetics, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, United Kingdom; Laboratory of Stem Cell Biology, Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germaine M.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263; Division of Genetics, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, United Kingdom; Laboratory of Stem Cell Biology, Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Lossie","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263; Division of Genetics, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, United Kingdom; Laboratory of Stem Cell Biology, Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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