{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T20:58:15Z","timestamp":1725224295091},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T00:00:00Z","timestamp":1358380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deletion of chr22q11 gives rise to velo\u2010cardio facial syndrome (VCFS) and increases schizophrenia risk. The source of this elevated risk although unknown could result from stochastic, environmental, or genetic factors, the latter encompassing a range of complexity from polygenic mechanisms to \u201csecond\u2010hit\u201d mutations. For this study we tested the two\u2010hit hypothesis where additional risk is conferred through a second CNV. We identified large (&gt;100\u2009kb) CNVs in 48 VCFS cases (23 with psychosis\u201425 without) and show in the psychotic VCFS group there is a significant (<jats:italic>P<\/jats:italic>\u2009=\u20090.02) increase in the average size of CNVs (354\u2013227\u2009kb). To identify second\u2010hit loci we focused on individuals possessing gene\u2010centric CNVs and through literature mining identified 4 (31%) psychotic VCFS individuals (n\u2009=\u200913) that overlapped loci previously implicated in neuropsychiatric disorders compared to 1 (10%) from the non\u2010psychotic VCFS individuals (n\u2009=\u200910). For replication 17 VCFS patients with schizophrenia from the molecular genetics of schizophrenia dataset were used to identify further CNVs. Thirteen individuals possessing gene\u2010centric CNVs were identified including 3 (23%) individuals possessing a potential second\u2010hit, taking the overall total in the psychotic VCFS group (n\u2009=\u200926) to 7 (27%) potential second\u2010hit loci. Notably a deletion in a psychotic VCFS patient at 2q23.1 hit the gene <jats:italic>MBD5<\/jats:italic> which when deleted gives rise to intellectual disability, epilepsy, and autistic features. Through this study we potentially extend this phenotypic spectrum to include schizophrenia. Our results suggest the two\u2010hit hypothesis may be relevant to a proportion of VCFS patients with psychosis but sample sizes are small and further studies warranted. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.32129","type":"journal-article","created":{"date-parts":[[2013,1,17]],"date-time":"2013-01-17T13:58:00Z","timestamp":1358431080000},"page":"177-182","source":"Crossref","is-referenced-by-count":21,"title":["Schizophrenia two\u2010hit hypothesis in velo\u2010cardio facial syndrome"],"prefix":"10.1002","volume":"162","author":[{"given":"Hywel J.","family":"Williams","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Monks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieran 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