{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:30:33Z","timestamp":1777635033900,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We report a case of hereditary bilateral retinoblastoma due to a\n                    <jats:italic>de novo<\/jats:italic>\n                    germline inversion on chromosome 13, resulting in disruption of the\n                    <jats:italic>RB1<\/jats:italic>\n                    gene. The patient is a 22\u2010month\u2010old female who initially presented to the emergency room at 11\u2009months of age with an erythematous left eye and leukocoria of the right eye. Computed tomography (CT) of the brain and orbits showed solid internal calcifications arising from the posterior globes concerning for bilateral retinoblastoma. Magnetic resonance imaging (MRI) of the brain and orbits confirmed bilateral retinoblastoma without associated pineal region or suprasellar mass. On initial examination under anesthesia, the right eye showed one tumor in the macula and two tumors in the inferior mid\u2010periphery. Sub\u2010retinal seeding extended to the inferior periphery. The left eye was enucleated and pathology showed leptomeningeal extension along the optic nerve extending to the surgical margin. The patient was treated on a non\u2010protocol treatment plan with five cycles of vincristine, carboplatin, etoposide, cyclophosphamide, and weekly intraventricular topotecan via Ommaya reservoir, followed by autologous stem cell rescue. Tumor analysis showed loss of pRB protein expression by immunohistochemistry and methylation copy number profiling showed several segmental gains and losses, including focal loss of\n                    <jats:italic>RB1<\/jats:italic>\n                    on 13q. A 123\u2010gene cancer predisposition germline panel using genome and exome sequencing initially did not identify any\n                    <jats:italic>RB1<\/jats:italic>\n                    single nucleotide variants or insertion\/deletions. Subsequent constitutional chromosome analysis for\n                    <jats:italic>RB1<\/jats:italic>\n                    showed a paracentric inversion between bands 13q14.2 and 13q31. Optical genome mapping (OGM) showed that the proximal breakpoint of the balanced inversion at 13q14.2 was within intron 17 of\n                    <jats:italic>RB1<\/jats:italic>\n                    , while the distal breakpoint at 13q31.3 did not interrupt any known genes of clinical significance. We review the various molecular techniques that aided in diagnosis of this patient and provide a summary of similar\n                    <jats:italic>RB1<\/jats:italic>\n                    \u2010disrupting structural variants reported in the literature.\n                  <\/jats:p>","DOI":"10.1002\/gcc.70120","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T06:27:09Z","timestamp":1775456829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimodal Cytogenetic and Molecular Approach for the Detection of a Constitutional Balanced Paracentric Inversion Disrupting\n                    <i>RB1<\/i>\n                    in an Infant With Bilateral Retinoblastoma"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-5835","authenticated-orcid":false,"given":"Arti S.","family":"Pandey","sequence":"first","affiliation":[{"name":"Division of Cancer Predisposition, Department of Oncology St Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexa","family":"Siskar","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim E.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Division of Cancer Predisposition, Department of Oncology St Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julieann C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew W.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute University of Tennessee  Memphis Tennessee USA"},{"name":"Department of Surgery St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad K.","family":"Eldomery","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-2610","authenticated-orcid":false,"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-1275","authenticated-orcid":false,"given":"Patrick R.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35101031"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70045-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1686"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102264"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101821"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(199910)14:4<283::AID-HUMU2>3.0.CO;2-J"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040754"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2021.08.014"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-200212000-00004"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.05.005"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102447"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083523"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3144"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10110879"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000004224"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1854-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes16070780"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes16080924"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00367-3"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02337"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-1063"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2024.101276"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.12.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.04.018"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-009-0042-1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.424728"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1076\/opge.22.1.1.2236"}],"container-title":["Genes, 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