{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:03:27Z","timestamp":1760148207988,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,9]],"date-time":"2023-04-09T00:00:00Z","timestamp":1680998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State of S\u00e3o Paulo Research Foundation","award":["#2012\/51799-6","#2018\/08890-9","#309782\/2020-1","#131248\/2021-9","001"],"award-info":[{"award-number":["#2012\/51799-6","#2018\/08890-9","#309782\/2020-1","#131248\/2021-9","001"]}]},{"name":"National Council for Scientific and Technological Development","award":["#2012\/51799-6","#2018\/08890-9","#309782\/2020-1","#131248\/2021-9","001"],"award-info":[{"award-number":["#2012\/51799-6","#2018\/08890-9","#309782\/2020-1","#131248\/2021-9","001"]}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["#2012\/51799-6","#2018\/08890-9","#309782\/2020-1","#131248\/2021-9","001"],"award-info":[{"award-number":["#2012\/51799-6","#2018\/08890-9","#309782\/2020-1","#131248\/2021-9","001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Insertions are rare balanced chromosomal rearrangements with an increased risk of imbalances for the offspring. Moreover, balanced rearrangements in individuals with abnormal phenotypes may be associated to the phenotype by different mechanisms. This study describes a three-generation family with a rare chromosomal insertion. G-banded karyotype, chromosomal microarray analysis (CMA), whole-exome sequencing (WES), and low-pass whole-genome sequencing (WGS) were performed. Six individuals had the balanced insertion [ins(9;15)(q33;q21.1q22.31)] and three individuals had the derivative chromosome 9 [der(9)ins(9;15)(q33;q21.1q22.31)]. The three subjects with unbalanced rearrangement showed similar clinical features, including intellectual disability, short stature, and facial dysmorphisms. CMA of these individuals revealed a duplication of 19.3 Mb at 15q21.1q22.31. A subject with balanced rearrangement presented with microcephaly, severe intellectual disability, absent speech, motor stereotypy, and ataxia. CMA of this patient did not reveal pathogenic copy number variations and low-pass WGS showed a disruption of the RABGAP1 gene at the 9q33 breakpoint. This gene has been recently associated with a recessive disorder, which is not compatible with the mode of inheritance in this patient. WES revealed an 88 bp deletion in the MECP2 gene, consistent with Rett syndrome. This study describes the clinical features associated with the rare 15q21.1\u2013q22.31 duplication and reinforces that searching for other genetic causes is warranted for individuals with inherited balanced chromosomal rearrangements and abnormal phenotypes.<\/jats:p>","DOI":"10.3390\/genes14040885","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare 15q21.1q22.31 Duplication Due to a Familial Chromosomal Insertion and Diagnostic Investigation in a Carrier of Balanced Chromosomal Rearrangement and Intellectual Disability"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-5498","authenticated-orcid":false,"given":"Carolina Gama","family":"Nascimento","sequence":"first","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana Rosa Marques","family":"Prota","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il\u00e1ria Cristina","family":"Sgardioli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samira","family":"Spineli-Silva","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilma L\u00facia Viguetti","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-0554","authenticated-orcid":false,"given":"Vera L\u00facia","family":"Gil-da-Silva-Lopes","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4027-8341","authenticated-orcid":false,"given":"T\u00e1rsis Paiva","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine\u2014Medical Genetics and Genomic Medicine, School of Medical Sciences, State University of Campinas, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"ref_1","first-page":"415","article-title":"Interchromosomal Insertions. 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PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169935"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/4\/885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:45Z","timestamp":1760123565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/4\/885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,9]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["genes14040885"],"URL":"https:\/\/doi.org\/10.3390\/genes14040885","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2023,4,9]]}}}