{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T16:40:25Z","timestamp":1779122425039,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>CNOT2<\/jats:italic> haploinsufficiency underlies a rare neurodevelopmental disorder named Intellectual Developmental disorder with NAsal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS, OMIM 618608). The condition clinically overlaps with chromosome 12q15 deletion syndrome, suggesting a major contribution of <jats:italic>CNOT2<\/jats:italic> haploinsufficiency to the latter. CNOT2 is a member of the CCR4\u2010NOT complex, which is a master regulator of multiple cellular processes, including gene expression, RNA deadenylation, and protein ubiquitination. To date, less than 20 pathogenic 12q15 microdeletions encompassing <jats:italic>CNOT2<\/jats:italic>, together with a single truncating variant of the gene, and two large intragenic deletions have been reported. Due to the small number of affected subjects described so far, the clinical profile of IDNADFS has not been fully delineated. Here we report five unrelated individuals, three of which carrying <jats:italic>de novo<\/jats:italic> intragenic <jats:italic>CNOT2<\/jats:italic> variants, one presenting with a multiexon intragenic deletion, and an additional case of 12q15 microdeletion syndrome. Finally, we assess the features of IDNADFS by reviewing published and present affected individuals and reevaluate the clinical phenotype of this neurodevelopmental disorder.<\/jats:p>","DOI":"10.1111\/cge.14247","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T02:24:35Z","timestamp":1665627875000},"page":"156-166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Delineation of the clinical profile of <scp><i>CNOT2<\/i><\/scp> haploinsufficiency and overview of the <scp>IDNADFS<\/scp> phenotype"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4766-7753","authenticated-orcid":false,"given":"Marcello","family":"Niceta","sequence":"first","affiliation":[{"name":"Genetics and Rare Diseases Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"},{"name":"Department of Pediatrics Sapienza University  Rome 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