{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:13:20Z","timestamp":1764195200363,"version":"3.46.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Chromosomes 3 and 8 harbor genes essential for neurodevelopment, skeletal formation, and metabolic regulation. We report a case of two half-siblings with neurodevelopmental delay and intellectual disability who inherited a derivative chromosome 3 from their asymptomatic mother. Chromosomal microarray analysis first identified a 7.12\u00a0Mb deletion in 3p26.3\u2013p26.1 and a 48.86\u00a0Mb duplication in 8q22.1\u2013q24.3, and findings were further characterized by whole genome sequencing and manual structural interpretation. The 3p deletion involved four pathogenic genes (\n                    <jats:italic>CHL1, CNTN6, CNTN4, ITPR1<\/jats:italic>\n                    ) associated with cognitive impairment, ataxia, and motor dysfunction. The 8q duplication affected 50 dosage-sensitive genes implicated in developmental and neurological disorders. Together, these chromosomal imbalances explain the siblings\u2019 phenotype and underscore the contribution of gene dosage effects to neurodevelopmental disease. This case highlights the utility of combining chromosomal microarray and genome sequencing in the diagnosis of complex rearrangements and emphasizes the importance of early genetic counseling and intervention.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2025.1662915","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:10:13Z","timestamp":1764195013000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: developmental delay and intellectual disability linked to a maternally inherited derivative chromosome 3 from a t(3;8) translocation"],"prefix":"10.3389","volume":"16","author":[{"given":"Andr\u00e9s","family":"Le\u00f3n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex S.","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lindstrand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlene","family":"Ek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa I.","family":"Romero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e1009906","DOI":"10.1371\/journal.pgen.1009906","article-title":"The good, the bad, and the ugly: evolutionary and pathological aspects of gene dosage alterations","volume":"17","author":"Basilicata","year":"2021","journal-title":"PLoS Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ejmg.2011.09.001","article-title":"A de novo 8q22.2-24.3 duplication in a patient with mild phenotype","volume":"55","author":"Concolino","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"618059","DOI":"10.3389\/fped.2021.618059","article-title":"Case report: a case report and literature review of 3p deletion syndrome","volume":"9","author":"Fu","year":"2021","journal-title":"Front Pediatr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1002\/ajmg.a.36006","article-title":"8q22.1 microdeletion syndrome: further delineation of the phenotype and gene responsible for cognitive impairment","author":"Hancarova","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"B5","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41576-020-0220-2","article-title":"Mechanisms of structural chromosomal rearrangements in clinical genetics","volume":"21","author":"Higgins","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.3390\/genes12111734","article-title":"Alternative lengthening of telomeres: lessons to be learned from telomeric DNA double-strand break repair","volume":"12","author":"Kruszewski","year":"2021","journal-title":"Genes"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e49","DOI":"10.1371\/journal.pgen.0010049","article-title":"Genomic disorders: molecular mechanisms for rearrangements and conveyed phenotypes","volume":"1","author":"Lupski","year":"2005","journal-title":"PLoS Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1002\/ccr3.4036","article-title":"Familiar del3p syndrome: the uncertainty of the prognosis. A case report","volume":"9","author":"Martins","year":"2021","journal-title":"Clin. Case Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"730375","DOI":"10.1155\/2014\/730375","article-title":"A rare interstitial duplication of 8q22.1-8q24.3 associated with syndromic bilateral cleft lip\/palate","volume":"2014","author":"Rezek","year":"2014","journal-title":"Case Rep. Dent."},{"key":"B15","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12915-017-0418-y","article-title":"Dosage-sensitive genes in evolution and disease","volume":"15","author":"Rice","year":"2017","journal-title":"BMC Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1002\/ajmg.a.36259","article-title":"3p deletion syndrome: description of a new case and narrowing of the critical region for intellectual disability and congenital heart defects","author":"Shoukier","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"B18","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13073-021-00855-5","article-title":"Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients","volume":"13","author":"Stranneheim","year":"2021","journal-title":"Genome Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0294236","DOI":"10.1371\/journal.pone.0294236","article-title":"SRplot: a free online platform for data visualization and graphing","volume":"18","author":"Tang","year":"2023","journal-title":"PLoS One"},{"key":"B20","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.tig.2013.04.004","article-title":"Gene dosage effects: nonlinearities, genetic interactions, and dosage compensation","volume":"29","author":"Veitia","year":"2013","journal-title":"Trends Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1146\/annurev-genom-083218-015151","article-title":"Copy number variation in human health, disease, and evolution","volume":"20","author":"Zhang","year":"2019","journal-title":"Annu. Rev. Genomics Hum. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1662915\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:10:14Z","timestamp":1764195014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2025.1662915\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":15,"alternative-id":["10.3389\/fgene.2025.1662915"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2025.1662915","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]},"article-number":"1662915"}}