{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:04:41Z","timestamp":1790787881943,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20\u201340 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G\/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.<\/jats:p>","DOI":"10.3390\/ijms22168611","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T22:40:31Z","timestamp":1628635231000},"page":"8611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-8982","authenticated-orcid":false,"given":"Kathleen","family":"Rooney","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada"},{"name":"Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Levy","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadegheh","family":"Haghshenas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-6606","authenticated-orcid":false,"given":"Jennifer","family":"Kerkhof","sequence":"additional","affiliation":[{"name":"Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rogaia","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Maternal-Infantile Department, University and Hospital of Perugia, 06129 Perugia, Italy"},{"name":"Pediatric Clinic, Department of Medicine, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Tedesco","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Maternal-Infantile Department, University and Hospital of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3608-6999","authenticated-orcid":false,"given":"Valentina","family":"Imperatore","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Maternal-Infantile Department, University and Hospital of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedea","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Maternal-Infantile Department, University and Hospital of Perugia, 06129 Perugia, Italy"},{"name":"Pediatric Clinic, Department of Medicine, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella Maria","family":"Squeo","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Di Venere","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Cara","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Medicine, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Verrotti","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Medicine, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5078-928X","authenticated-orcid":false,"given":"Giuseppe","family":"Merla","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-6702","authenticated-orcid":false,"given":"Matthew L.","family":"Tedder","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara R.","family":"DuPont","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekim","family":"Sadikovic","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada"},{"name":"Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Maternal-Infantile Department, University and Hospital of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MD.0b013e3182060469","article-title":"Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome\/velocardiofacial syndrome)","volume":"90","author":"Sullivan","year":"2011","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/hmg\/5.6.789","article-title":"A transcription map of the DiGeorge and velo-cardio-facial syndrome minimal critical region on 22q11","volume":"5","author":"Gong","year":"1996","journal-title":"Hum. 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