{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T05:24:05Z","timestamp":1761110645668,"version":"3.40.5"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T00:00:00Z","timestamp":1652486400000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>When a de novo balanced reciprocal translocation is identified in patients with multiple congenital abnormalities, attempts are often made to infer the relationship between the phenotype of the patient and genes in the proximity of the breakpoint. Here, we report a patient with intellectual disability, atrial septal defect, syndactyly, and cleft lip and palate who had an \u201capparently balanced\u201d de novo reciprocal translocation t(4:18)(q31;q11.2) as well as a 7\u2010Mb cryptic deletion spanning the <jats:italic>HOXD<\/jats:italic> cluster on chromosome 2q31 that was unrelated to the reciprocal translocation. Further analysis using a nanopore long\u2010read sequencer showed complex rearrangements on both derivative chromosomes 4 and 18 and the deleted chromosome 2. First, the <jats:italic>TLL1<\/jats:italic> locus, which is associated with atrial septal defect, was disrupted by the rearrangement involving chromosome 4. Second, the deleted interval at 2q31 included the entire <jats:italic>HOXD<\/jats:italic> cluster, the deletion of which is known to cause toe syndactyly, and the <jats:italic>DLX1<\/jats:italic> and <jats:italic>DLX2<\/jats:italic> loci, which are responsible for cleft lip and palate. Among the haplo\u2010sensitive genes within the deleted interval on 2q31, only the <jats:italic>RAPGEF4<\/jats:italic> gene is known to be associated with an autistic phenotype. Hence, most of the clinical features of the patient could be ascribed to specific genomic rearrangements. We have shown the effectiveness of long\u2010read sequencing in defining, in detail, the likely effects of an apparently balanced translocation and cryptic deletion. The results of the present analysis suggest the possibility of phenotypic prediction through a detailed analysis of structural abnormalities, including balanced translocations and deletions.<\/jats:p>","DOI":"10.1002\/ajmg.a.62777","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T12:20:39Z","timestamp":1652530839000},"page":"2472-2478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deciphering complex rearrangements at the breakpoint of an apparently balanced reciprocal translocation t(4:18)(q31;q11.2)dn and at a cryptic deletion: Further evidence of <scp><i>TLL1<\/i><\/scp> as a causative gene for atrial septal defect"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4039-8899","authenticated-orcid":false,"given":"Mamiko","family":"Yamada","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8122-7180","authenticated-orcid":false,"given":"Hisato","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyuki","family":"Miya","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6798-8151","authenticated-orcid":false,"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo 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