{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:29:59Z","timestamp":1779179399570,"version":"3.51.4"},"reference-count":35,"publisher":"Cold Spring Harbor Laboratory","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Genetic studies grounded on monogenic paradigms have accelerated both gene discovery and molecular diagnosis. At the same time, complex genomic rearrangements are also appreciated as potent drivers of disease pathology. Here, we report two male siblings with a dysmorphic face, ambiguous genitalia, intellectual disability, and speech delay. Through quad-based whole-exome sequencing and concomitant molecular cytogenetic testing, we identified two copy-number variants (CNVs) in both affected individuals likely arising from a balanced translocation: a 13.5-Mb duplication on Chromosome 16 (16q23.1 \u2192 16qter) and a 7.7-Mb deletion on Chromosome 5 (5p15.31 \u2192 5pter), as well as a hemizygous missense variant in<jats:italic>CXorf36<\/jats:italic>(also known as<jats:italic>DIA1R<\/jats:italic>). The 5p terminal deletion has been associated previously with speech delay, whereas craniofacial dysmorphia and genital\/urinary anomalies have been reported in patients with a terminal duplication of 16q. However, dosage changes in either genomic region alone could not account for the overall clinical presentation in our family; functional testing of<jats:italic>CXorf36<\/jats:italic>in zebrafish did not induce defects in neurogenesis or the craniofacial skeleton. Notably, literature and database analysis revealed a similar dosage disruption in two siblings with extensive phenotypic overlap with our patients. Taken together, our data suggest that dosage perturbation of genes within the two chromosomal regions likely drives the syndromic manifestations of our patients and highlight how multiple genetic lesions can contribute to complex clinical pathologies.<\/jats:p>","DOI":"10.1101\/mcs.a000703","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T18:35:55Z","timestamp":1455561355000},"page":"a000703","source":"Crossref","is-referenced-by-count":2,"title":["A t(5;16) translocation is the likely driver of a syndrome with ambiguous genitalia, facial dysmorphism, intellectual disability, and speech delay"],"prefix":"10.1101","volume":"2","author":[{"given":"Ay\u015feg\u00fcl","family":"Ozant\u00fcrk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica E.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aniko","family":"Sabo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjan M.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Muzny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon","family":"Dugan-Perez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik A.","family":"Sistermans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00f6ksal R.","family":"\u00d6zg\u00fcl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilek","family":"Yaln\u0131zoglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra","family":"Serdaroglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Dursun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Katsanis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"246","published-online":{"date-parts":[[2015,12,18]]},"reference":[{"key":"2021112506093553000_2.2.a000703.1","doi-asserted-by":"crossref","first-page":"e14534","DOI":"10.1371\/journal.pone.0014534","article-title":"DIA1R is an X-linked gene related to Deleted in Autism-1","volume":"6","year":"2011","journal-title":"PLoS One"},{"key":"2021112506093553000_2.2.a000703.2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-7-r68"},{"key":"2021112506093553000_2.2.a000703.3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10159"},{"key":"2021112506093553000_2.2.a000703.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.05.003"},{"key":"2021112506093553000_2.2.a000703.5","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176925.114"},{"key":"2021112506093553000_2.2.a000703.6","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/ajmg.b.10740","article-title":"Molecular characterization of partial trisomy 16q24.1-qter: clinical report and review of the literature","volume":"113","year":"2002","journal-title":"Am J Med Genet"},{"key":"2021112506093553000_2.2.a000703.7","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.114.168211"},{"key":"2021112506093553000_2.2.a000703.8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-8"},{"key":"2021112506093553000_2.2.a000703.9","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100892"},{"key":"2021112506093553000_2.2.a000703.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.09.010"},{"key":"2021112506093553000_2.2.a000703.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2012.04.006"},{"key":"2021112506093553000_2.2.a000703.12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejmg.2014.02.005","article-title":"A three-generation family with terminal microdeletion involving 5p15.33-32 due to a whole-arm 5;15 chromosomal translocation with a steady phenotype of atypical cri du chat syndrome","volume":"57","year":"2014","journal-title":"Eur J Med Genet"},{"key":"2021112506093553000_2.2.a000703.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.005"},{"key":"2021112506093553000_2.2.a000703.14","first-page":"1404","article-title":"Evidence for a distinct region causing a cat-like cry in patients with 5p deletions","volume":"56","year":"1995","journal-title":"Am J Hum Genet"},{"key":"2021112506093553000_2.2.a000703.15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200730"},{"key":"2021112506093553000_2.2.a000703.16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200395"},{"key":"2021112506093553000_2.2.a000703.17","doi-asserted-by":"publisher","DOI":"10.1038\/nature11091"},{"key":"2021112506093553000_2.2.a000703.18","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/ajmg.a.33400","article-title":"A t(5;16)(p15.32;q23.3) generating 16q23.3 \u2192 qter duplication and 5p15.32 \u2192 pter deletion in two siblings with mental retardation, dysmorphic features, and speech delay","volume":"152A","year":"2010","journal-title":"Am J Med Genet A"},{"key":"2021112506093553000_2.2.a000703.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.05.010"},{"key":"2021112506093553000_2.2.a000703.20","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"2021112506093553000_2.2.a000703.21","doi-asserted-by":"publisher","DOI":"10.1101\/gr.138115.112"},{"key":"2021112506093553000_2.2.a000703.22","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32988"},{"key":"2021112506093553000_2.2.a000703.23","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/humu.22813","article-title":"Comparison of exome and genome sequencing technologies for the complete capture of protein-coding regions","volume":"36","year":"2015","journal-title":"Hum Mutat"},{"key":"2021112506093553000_2.2.a000703.24","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2454"},{"key":"2021112506093553000_2.2.a000703.25","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"2021112506093553000_2.2.a000703.26","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.ajhg.2014.03.017","article-title":"Recurrent CNVs and SNVs at the NPHP1 locus contribute pathogenic alleles to Bardet\u2013Biedl syndrome","volume":"94","year":"2014","journal-title":"Am J Hum Genet"},{"key":"2021112506093553000_2.2.a000703.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.004"},{"key":"2021112506093553000_2.2.a000703.28","doi-asserted-by":"publisher","DOI":"10.1038\/ng.499"},{"key":"2021112506093553000_2.2.a000703.29","doi-asserted-by":"crossref","unstructured":"Niederriter AR , Davis EE , Golzio C , Oh EC , Tsai IC , Katsanis N . 2013. In vivo modeling of the morbid human genome using Danio rerio . J Vis Exp e50338.","DOI":"10.3791\/50338"},{"key":"2021112506093553000_2.2.a000703.30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1186802"},{"key":"2021112506093553000_2.2.a000703.31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-092010-110715"},{"key":"2021112506093553000_2.2.a000703.32","doi-asserted-by":"publisher","DOI":"10.1038\/ng754"},{"key":"2021112506093553000_2.2.a000703.33","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199712)20:4<399::AID-GCC12>3.0.CO;2-I"},{"key":"2021112506093553000_2.2.a000703.34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306555"},{"key":"2021112506093553000_2.2.a000703.35","doi-asserted-by":"publisher","DOI":"10.1086\/427762"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a000703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T11:09:39Z","timestamp":1718363379000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a000703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,18]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,3,1]]},"published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1101\/mcs.a000703"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a000703","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,18]]}}}