{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:32:38Z","timestamp":1790195558301,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T00:00:00Z","timestamp":1665878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana Ricerca sul Cancro IG","award":["IG 2020 N. 24405 (AR)"],"award-info":[{"award-number":["IG 2020 N. 24405 (AR)"]}]},{"name":"Associazione Italiana Ricerca sul Cancro IG","award":["MIRIAM"],"award-info":[{"award-number":["MIRIAM"]}]},{"name":"\u201cProgetti competitivi intraAteneo\u201d Programma V:ALERE (VAnviteLli pEr la RicErca)","award":["IG 2020 N. 24405 (AR)"],"award-info":[{"award-number":["IG 2020 N. 24405 (AR)"]}]},{"name":"\u201cProgetti competitivi intraAteneo\u201d Programma V:ALERE (VAnviteLli pEr la RicErca)","award":["MIRIAM"],"award-info":[{"award-number":["MIRIAM"]}]},{"name":"Italian Ministry of University and Research","award":["IG 2020 N. 24405 (AR)"],"award-info":[{"award-number":["IG 2020 N. 24405 (AR)"]}]},{"name":"Italian Ministry of University and Research","award":["MIRIAM"],"award-info":[{"award-number":["MIRIAM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Silver\u2013Russell syndrome is an imprinting disorder characterised by pre- and post-natal growth retardation and several heterogeneous molecular defects affecting different human genomic loci. In the majority of cases, the molecular defect is the loss of methylation (LOM) of the H19\/IGF2 differentially methylated region (DMR, also known as IC1) at the telomeric domain of the 11p15.5 imprinted genes cluster, which causes the altered expression of the growth controlling genes, IGF2 and H19. Very rarely, the LOM also affects the KCNQ1OT1 DMR (also known as IC2) at the centromeric domain, resulting in an SRS phenotype by an unknown mechanism. In this study, we report on two cases with SRS features and a LOM of either IC1 and IC2. In one case, this rare and complex epimutation was secondary to a de novo mosaic in cis maternal duplication, involving the entire telomeric 11p15.5 domain and part of the centromeric domain but lacking CDKN1C. In the second case, neither the no 11p15.5 copy number variant nor the maternal-effect subcortical maternal complex (SCMC) variant were found to be associated with the epimutation, suggesting that it arose as a primary event. Our findings further add to the complexity of the molecular genetics of SRS and indicate how the LOM in both 11p15.5 DMRs may result from different molecular mechanisms.<\/jats:p>","DOI":"10.3390\/genes13101875","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:04:55Z","timestamp":1665965095000},"page":"1875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Different Mechanisms Cause Hypomethylation of Both H19 and KCNQ1OT1 Imprinted Differentially Methylated Regions in Two Cases of Silver\u2013Russell Syndrome Spectrum"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-9847","authenticated-orcid":false,"given":"Francesco","family":"Passaretti","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"},{"name":"U.O.C. Medical Genetics, Department of Translational Medical Sciences, A.O.U. Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8835-5567","authenticated-orcid":false,"given":"Laura","family":"Pignata","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Vitiello","sequence":"additional","affiliation":[{"name":"U.O.C. Medical Genetics, Department of Translational Medical Sciences, A.O.U. Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7514-5683","authenticated-orcid":false,"given":"Viola","family":"Alesi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"D\u2019Elia","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cecere","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Institute of Genetics and Biophysics (IGB) \u201cAdriano Buzzati-Traverso\u201d, Consiglio Nazionale delle Ricerche (CNR), 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9192-1232","authenticated-orcid":false,"given":"Fabio","family":"Acquaviva","sequence":"additional","affiliation":[{"name":"U.O.S. Medical Genetics, Pediatrics of Chronic and Multifactorial Diseases, A.O.R.N. Santobono-Pausilipon, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"De Brasi","sequence":"additional","affiliation":[{"name":"U.O.S. Medical Genetics, Pediatrics of Chronic and Multifactorial Diseases, A.O.R.N. Santobono-Pausilipon, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-3576","authenticated-orcid":false,"given":"Andrea","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Institute of Genetics and Biophysics (IGB) \u201cAdriano Buzzati-Traverso\u201d, Consiglio Nazionale delle Ricerche (CNR), 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-0356","authenticated-orcid":false,"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"},{"name":"U.O.C. Medical Genetics, Department of Translational Medical Sciences, A.O.U. Federico II, 80131 Naples, Italy"},{"name":"CEINGE Advanced Biotechnology, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-3021","authenticated-orcid":false,"given":"Flavia","family":"Cerrato","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrendo.2016.138","article-title":"Diagnosis and management of Silver\u2013Russell syndrome: First international consensus statement","volume":"13","author":"Wakeling","year":"2016","journal-title":"Nat. Rev. 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Epigenet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1875\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:18Z","timestamp":1760144118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,16]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["genes13101875"],"URL":"https:\/\/doi.org\/10.3390\/genes13101875","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,16]]}}}