{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:30:25Z","timestamp":1777415425617,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"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":["Congenital Anomalies"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chimeric transcripts are formed by chromosomal aberrations. Little is known about the role of chimeric transcripts in the pathogenesis of birth defects. We reanalyzed RNA\u2010seq data in alignment map files from the peripheral blood of 56 patients in whom the diagnoses could not be confirmed by standard exome analysis and transcriptome analysis to screen for chimeric transcripts using a dedicated software, ChimPipe. Chimeric analysis led to a diagnosis in two of the 56 patients: (a) the first patient had a chimeric transcript spanning the causative gene <jats:italic>ZEB2<\/jats:italic> and the <jats:italic>GTDC1<\/jats:italic> gene in its neighboring locus. RNA\u2010seq revealed reads spanning exon 5 of <jats:italic>ZEB2<\/jats:italic> and exon 7 of <jats:italic>GTDC1<\/jats:italic>. Whole genome sequencing revealed a 436\u2010kb deletion spanning intron 4 of <jats:italic>ZEB2<\/jats:italic> and intron 7 of <jats:italic>GTDC1<\/jats:italic> and the diagnosis of Mowat\u2010Wilson syndrome was made. (b) The second patient had a chimeric transcript spanning the causative gene <jats:italic>KCNK9<\/jats:italic> and the <jats:italic>TRAPPC9<\/jats:italic> gene in its neighboring locus. RNA\u2010seq revealed reads spanning exon 21 of <jats:italic>TRAPPC9<\/jats:italic> and exon 1 of <jats:italic>KCNK9<\/jats:italic>. Whole genome sequencing revealed a 186\u2010kb deletion spanning intron 20 of <jats:italic>TRAPPC9<\/jats:italic> and intron 1 of <jats:italic>KCNK9<\/jats:italic> in this patient. <jats:italic>KCNK9<\/jats:italic> gene is a maternally expressed imprinted gene. The diagnosis of Birk\u2010Barel syndrome was made. Thus, both patients had chimeric transcripts that were directly involved in the pathogenesis of the birth defects. The approach reported herein, of detecting chimeric transcripts from RNA\u2010seq data, is unique in that the approach does not rely on any prior information on the presence of genomic deletion.<\/jats:p>","DOI":"10.1111\/cga.12400","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T04:20:14Z","timestamp":1603945214000},"page":"76-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Role of chimeric transcript formation in the pathogenesis of birth defects"],"prefix":"10.1111","volume":"61","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"}]},{"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":"Akiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Juntendo University Urayasu Hospital  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"},{"name":"Department of Pediatrics, Central Hospital Aichi Developmental Disability Center  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo 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