{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T19:53:28Z","timestamp":1759694008305,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:00:00Z","timestamp":1550188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["Research on Rare and Intractable Diseases"],"award-info":[{"award-number":["Research on Rare and Intractable Diseases"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18ek0109301"],"award-info":[{"award-number":["JP18ek0109301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>Chromosome 12q15 microdeletion syndrome is characterized by intellectual disability and dysmorphic facial features, but the associations between each of the deleted genes and the phenotypes of 12q15 microdeletion syndrome remain unclear. Recently, the smallest region of overlap in 16 previously reported patients was used to define three candidate genes for the 12q15 microdeletion syndrome: <jats:italic>CNOT2<\/jats:italic>, <jats:italic>KCNMB4<\/jats:italic>, and <jats:italic>PTPRB<\/jats:italic>. Among these three candidate genes, <jats:italic>CNOT2<\/jats:italic> maintains the structural integrity of the carbon catabolite repressor 4 (CCR4)\u2010negative on TATA (NOT) complex, which plays a key role in regulating global gene expression, and is essential for the enzymatic activity of the CCR4\u2010NOT complex. Disruption of the CCR4\u2010NOT complex results in dysregulation of global gene expression, and is associated with various human disease processes, including neuronal diseases. Therefore, <jats:italic>CNOT2<\/jats:italic> haploinsufficiency might account for the neurological features of the 12q15 microdeletion syndrome. Herein, we document a 12\u2010year<jats:bold>\u2010<\/jats:bold>old female patient with mild intellectual disability and multiple structural abnormalities including cleft lip and palate and 2\u20133 toe syndactyly. She exhibited dysmorphic facial features such as upslanting and short palpebral fissures, micrognathia, low\u2010set ears, and hypoplastic antihelix. A microarray analysis showed a de novo 1.32\u2010Mb deletion within 12q15 that included <jats:italic>CNOT2<\/jats:italic> and 14 other genes. Remapping of the 12q15 deletion region in the 16 previously reported patients together with that in the newly identified patient indicated that <jats:italic>CNOT2<\/jats:italic> is the only gene that is commonly deleted. These findings suggest that <jats:italic>CNOT2<\/jats:italic> is the prime candidate for the neurological phenotypes of the 12q15 microdeletion syndrome.<\/jats:p>","DOI":"10.1002\/ajmg.a.61068","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T11:11:03Z","timestamp":1550229063000},"page":"659-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>CNOT2<\/i> as the critical gene for phenotypes of 12q15 microdeletion syndrome"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-7686","authenticated-orcid":false,"given":"Tomoko","family":"Uehara","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo 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