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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"<jats:p>\n                    The investigation of congenital imprinting disorders (CIDs) provides opportunities to elucidate the molecular mechanisms and role of genomic imprinting in development and human disease. Beckwith\u2013Wiedemann spectrum (BWSp) is a prototypic CID resulting from genetic and epigenetic alterations of imprinted genes at chromosome 11p15.5. In up to a quarter of individuals with BWSp, the epigenetic alterations are not confined to 11p15.5 imprinting control regions but also involve other imprinted gene clusters (multilocus imprinting disturbance; MLID). In a consanguineous family with two children diagnosed with BWSp and MLID, the affected individuals were homozygous for a missense variant in\n                    <jats:italic toggle=\"yes\">UHRF1<\/jats:italic>\n                    , a gene previously implicated in the maintenance of DNA methylation. To investigate whether the\n                    <jats:italic toggle=\"yes\">UHRF1<\/jats:italic>\n                    c. 2001G&gt;C, p.(Lys667Asn) missense substitution predisposes to abnormal establishment\/maintenance of genomic imprinting patterns, a genetically engineered mouse model with a\n                    <jats:italic toggle=\"yes\">Uhrf1<\/jats:italic>\n                    p.(Lys661Asn) variant was developed. Mice homozygous for the variant born to heterozygous mothers did not display an abnormal phenotype, but homozygotes born to healthy homozygous mothers displayed a range of phenotypes including prenatal lethality. Also, MLID was observed in affected mouse embryos. These findings are consistent with biallelic\n                    <jats:italic toggle=\"yes\">UHRF1<\/jats:italic>\n                    variants in affected individuals resulting in an autosomal recessively inherited cause of MLID in humans and expand the range of epigenetic disorders associated with\n                    <jats:italic toggle=\"yes\">UHRF1.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1073\/pnas.2505884122","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T19:00:32Z","timestamp":1755543632000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Germline variants in\n                    <i>UHRF1<\/i>\n                    are associated with multilocus imprinting disturbance in humans and mice"],"prefix":"10.1073","volume":"122","author":[{"given":"Eguzkine","family":"Ochoa","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine, University of 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