{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T20:32:48Z","timestamp":1769286768706,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by NF2 point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions\u2019 pathogenic effects at the genetic and epigenetic levels are currently unknown. We here report on 22q12 microdeletions\u2019 characterization in three NF2 patients with different phenotype complexities. A possible effect of the position was investigated by in silico analysis of 22q12 topologically associated domains (TADs) and regulatory elements, and by expression analysis of 12 genes flanking patients\u2019 deletions. A 147 Kb microdeletion was identified in the patient with the mildest phenotype, while two large deletions of 561 Kb and 1.8 Mb were found in the other two patients, showing a more severe symptomatology. The last two patients displayed intellectual disability, possibly related to AP1B1 gene deletion. The microdeletions change from one to five TADs, and the 22q12 chromatin regulatory landscape, according to the altered expression levels of four deletion-flanking genes, including PIK3IP1, are likely associated with an early ischemic event occurring in the patient with the largest deletion. Our results suggest that the identification of the deletion extent can provide prognostic markers, predictive of NF2 phenotypes, and potential therapeutic targets, thus overall improving patient management.<\/jats:p>","DOI":"10.3390\/ijms231710017","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4558-8376","authenticated-orcid":false,"given":"Viviana","family":"Tritto","sequence":"first","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4744-9377","authenticated-orcid":false,"given":"Marica","family":"Eoli","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Neuro-Oncologia Molecolare, Fondazione IRCCS, Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosina","family":"Paterra","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Neuro-Oncologia Molecolare, Fondazione IRCCS, Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-4085","authenticated-orcid":false,"given":"Serena","family":"Redaelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-474X","authenticated-orcid":false,"given":"Marco","family":"Moscatelli","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Neuroradiologia, Fondazione IRCCS, Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-7845","authenticated-orcid":false,"given":"Francesco","family":"Rusconi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-8467","authenticated-orcid":false,"given":"Paola","family":"Riva","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ajmg.a.33139","article-title":"Birth Incidence and Prevalence of Tumor-Prone Syndromes: Estimates from a UK Family Genetic Register Service","volume":"152","author":"Evans","year":"2010","journal-title":"Am. 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