{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:53:03Z","timestamp":1788335583505,"version":"build-2803163510"},"reference-count":42,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytogenet Genome Res"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Constitutional complex chromosomal rearrangements (CCRs) are considered rare cytogenetic events. Most apparently balanced CCRs are de novo and are usually found in patients with abnormal phenotypes. High-resolution techniques are unveiling genomic imbalances in a great percentage of these cases. In this paper, we report a patient with growth and developmental delay, dysmorphic features, nervous system anomalies (pachygyria, hypoplasia of the corpus callosum and cerebellum), a marked reduction in the ossification of the cranial vault, skull base sclerosis, and cardiopathy who presents a CCR with 9 breakpoints involving 4 chromosomes (3, 6, 8 and 14) and a 0.6-Mb deletion in 14q24.1. Although the only genomic imbalance revealed by the array technique was a deletion, the clinical phenotype of the patient most likely cannot be attributed exclusively to haploinsufficiency. Other events must also be considered, including the disruption of critical genes and position effects. A combination of several different investigative approaches (G-banding, FISH with different probes and SNP array techniques) was required to describe this CCR in full, suggesting that CCRs may be more frequent than initially thought. Additionally, we propose that a chain chromosome breakage mechanism may have occurred as a single rearrangement event resulting in this CCR. This study demonstrates the importance of applying different cytogenetic and molecular techniques to detect subtle rearrangements and to delineate the rearrangements at a more accurate level, providing a better understanding of the mechanisms involved in CCR formation and a better correlation with phenotype.<\/jats:p>","DOI":"10.1159\/000353302","type":"journal-article","created":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T12:08:29Z","timestamp":1372680509000},"page":"317-323","source":"Crossref","is-referenced-by-count":6,"title":["A Complex Chromosome Rearrangement Involving Four Chromosomes, Nine Breakpoints and a Cryptic 0.6-Mb Deletion in a Boy with Cerebellar Hypoplasia and Defects in Skull Ossification"],"prefix":"10.1159","volume":"141","author":[{"given":"R.S.","family":"Guilherme","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.C.S.P.","family":"Cernach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.E.","family":"Sfakianakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.S.","family":"Takeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.M.M.","family":"Nardozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.S.","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Liehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.I.","family":"Melaragno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2013,6,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.02.012"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320530311"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.11.858"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.suppl_1.45"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8166-5-5"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.052787"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8166-2-15"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/35093500"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.120"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.126.9.1301"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32059"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8417-1-4"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000327"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/ng1394"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1086\/426833"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.037"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33581"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.052308.093131"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(98)01555-8"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010049"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35220"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050453"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608375200"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.13.12108"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-082509-141651"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01116.x"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901401116"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.01.004"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33302"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmr010"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199811)18:11<1174::AID-PD411>3.0.CO;2-H"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1248-x"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.05.011"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201977"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/nature05723"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1101\/gr.122986.111"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.055"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.03.013"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-S1-S1"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1086\/429252"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2008.950550"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1038\/ng.399"}],"container-title":["Cytogenetic 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