{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:41:22Z","timestamp":1770064882096,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AssiGulliver Italian Association"},{"name":"Fondazione Sardegna"},{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>An increasing amount of evidence indicates the critical role of the NSD1 gene in Sotos syndrome (SoS), a rare genetic disease, and in tumors. Molecular mechanisms affected by NSD1 mutations are largely uncharacterized. In order to assess the impact of NSD1 haploinsufficiency in the pathogenesis of SoS, we analyzed the gene expression profile of fibroblasts isolated from the skin samples of 15 SoS patients and of 5 healthy parents. We identified seven differentially expressed genes and five differentially expressed noncoding RNAs. The most upregulated mRNA was stratifin (SFN) (fold change, 3.9, Benjamini\u2013Hochberg corrected p &lt; 0.05), and the most downregulated mRNA was goosecoid homeobox (GSC) (fold change, 3.9, Benjamini\u2013Hochberg corrected p &lt; 0.05). The most upregulated lncRNA was lnc-C2orf84-1 (fold change, 4.28, Benjamini\u2013Hochberg corrected p &lt; 0.001), and the most downregulated lncRNA was Inc-C15orf57 (fold change, \u22120.7, Benjamini\u2013Hochberg corrected p &lt; 0.05). A gene set enrichment analysis reported the enrichment of genes involved in the KRAS and E2F signaling pathways, splicing regulation and cell cycle G2\/M checkpoints. Our results suggest that NSD1 is involved in cell cycle regulation and that its mutation can induce the down-expression of genes involved in tumoral and neoplastic differentiation. The results contribute to defining the role of NSD1 in fibroblasts for the prevention, diagnosis and control of SoS.<\/jats:p>","DOI":"10.3390\/life12070988","type":"journal-article","created":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T22:50:46Z","timestamp":1656888646000},"page":"988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["NSD1 Mutations in Sotos Syndrome Induce Differential Expression of Long Noncoding RNAs, miR646 and Genes Controlling the G2\/M Checkpoint"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-3576","authenticated-orcid":false,"given":"Giuseppina","family":"Conteduca","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6010-5619","authenticated-orcid":false,"given":"Davide","family":"Cangelosi","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-4325","authenticated-orcid":false,"given":"Simona","family":"Coco","sequence":"additional","affiliation":[{"name":"Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Malacarne","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-3953","authenticated-orcid":false,"given":"Chiara","family":"Baldo","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Arado","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-5803","authenticated-orcid":false,"given":"Rute","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3516-2379","authenticated-orcid":false,"given":"Barbara","family":"Testa","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-865X","authenticated-orcid":false,"given":"Domenico A.","family":"Coviello","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1093\/emboj\/17.12.3398","article-title":"Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators","volume":"17","author":"Huang","year":"1998","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40417","DOI":"10.1074\/jbc.M104765200","article-title":"Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells","volume":"276","author":"Wang","year":"2001","journal-title":"J. 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