biostudies-literatureOchoa EKing Abdullah University of Science and Technology (KAUST)Marie Curie Initial Training Network AwardNIHR | NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC)EpiGenRare MRC Rare Diseases Node fundingAlan Turing Institute under the Engineering and Physical Sciences Research CouncilRosetrees Trust (Rosetrees)Medical Research Counce2505884122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12403135biostudies-literatureUnknown122(34)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-Wiedemann 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 <i>UHRF1</i>, a gene previously implicated in the maintenance of DNA methylation. To investigate whether theProceedings of the National Academy of Sciences of the United States of AmericaGermline variants in &lt;i&gt;UHRF1&lt;/i&gt; are associated with multilocus imprinting disturbance in humans and mice.PMC12403135EP/N510129/1INGENIUMMRC_MC_UU_12012/4MR/Y008170/1PhDPlusOSR-GRG2019-4043BRC-1215-20014Docquier FRodger FClark GOchoa EBottolo LConstancia MYngvadottir BLan-Leung BFoster-Hall DZvetkova IMartin EHobson EToribio ATakahashi NIssa MFerguson-Smith ACLiv Lee SMaher ERFischle WfalseGermline variants in &lt;i&gt;UHRF1&lt;/i&gt; are associated with multilocus imprinting disturbance in humans and mice.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-Wiedemann 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 <i>UHRF1</i>, a gene previously implicated in the maintenance of DNA methylation. To investigate whether the2025-01-01T00:00:00Z2025 Aug2026-07-15T06:27:09.509Z2026-07-01T03:07:24.878ZS-EPMC124031354082513110.1073/pnas.2505884122