{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:23:14Z","timestamp":1761718994812,"version":"3.40.5"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J intellect Disabil Res"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Complex chromosomal rearrangements (CCRs) are structural rearrangements involving more than three chromosomes or having more than two breaks; approximately 70% are not associated with any clinical phenotype. Here, we describe a CCR segregating in a two\u2010generation family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A 4\u2010year\u2010old male was evaluated for developmental delay, mild intellectual disability and epicanthus. Karyotype, fluorescence in situ hybridisation (FISH) analysis and array comparative genomic hybridisation (aCGH) analysis were performed on the patient and of all family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Array CGH analysis of the proband detected two non\u2010contiguous genomic gains of chromosome 2 at bands q32.3q33.2 and bands q36.1q36.3. Both karyotype and FISH analysis revealed a recombinant chromosome 2 with a direct insertion of regions q32.3q33.2 and q36.1q36.3 into region q12. Both of these regions were also present in their original location. Karyotype and FISH analysis of the father revealed a de novo direct insertion of regions q32.3q33.2 and q36.1q36.3 into region q12. Moreover, a de novo balanced translocation involving the q arm of the same chromosome 2 and the p arm of chromosome 10 was observed in the father of the proband. The single nucleotide polymorphism (SNP) array analysis and haplotype reconstruction confirmed the paternal origin of the duplications. Karyotype, FISH analysis and array CGH analysis of other family members were all normal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This report underlines the importance of using different methods to correctly evaluate the origin and the structure of CCRs in order to provide an appropriate management of the patients and a good estimation of the reproductive risk of the family.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jir.12797","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T01:35:36Z","timestamp":1604367336000},"page":"113-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Complex genomic alterations and intellectual disability: an interpretative challenge"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-7941","authenticated-orcid":false,"given":"R.","family":"Silipigni","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Milani","sequence":"additional","affiliation":[{"name":"Pediatric Highly Intensive Care Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Tolva","sequence":"additional","affiliation":[{"name":"Pediatric Highly Intensive Care Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Monfrini","sequence":"additional","affiliation":[{"name":"Neurology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"},{"name":"Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Giacobbe","sequence":"additional","affiliation":[{"name":"Child and Adolescent Neuropsychiatric Service (UONPIA) Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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