{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:34:44Z","timestamp":1768440884951,"version":"3.49.0"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T00:00:00Z","timestamp":1547078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["GA.012.14N"],"award-info":[{"award-number":["GA.012.14N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We describe a patient presenting with pachygyria, epilepsy, developmental delay, short stature, failure to thrive, facial dysmorphisms, and multiple osteochondromas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The patient underwent extensive genetic testing and analysis in an attempt to diagnose the cause of his condition. Clinical testing included metaphase karyotyping, array comparative genomic hybridization, direct sequencing and multiplex ligation\u2010dependent probe amplification and trio\u2010based exome sequencing. Subsequently, research\u2010based whole transcriptome sequencing was conducted to determine whether it might shed light on the undiagnosed phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical exome sequencing of patient and parent samples revealed a maternally inherited splice\u2010site variant in the doublecortin (<jats:italic><jats:styled-content style=\"fixed-case\">DCX<\/jats:styled-content><\/jats:italic>) gene that was classified as likely pathogenic and diagnostic of the patient's neurological phenotype. Clinical array comparative genome hybridization analysis revealed a 16p13.3 deletion that could not be linked to the patient phenotype based on affected genes. Further clinical testing to determine the cause of the patient's multiple osteochondromas was unrevealing despite extensive profiling of the most likely causative genes, <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic>, including mutation screening by direct sequence analysis and multiplex ligation\u2010dependent probe amplification. Whole transcriptome sequencing identified a <jats:italic><jats:styled-content style=\"fixed-case\">SAMD<\/jats:styled-content>12\u2010<jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> fusion transcript that could have resulted from a chromosomal deletion, leading to the loss of <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> function. Re\u2010review of the clinical array comparative genomic hybridization results indicated a possible unreported mosaic deletion affecting the <jats:italic><jats:styled-content style=\"fixed-case\">SAMD<\/jats:styled-content>12<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> genes that corresponded precisely to the introns predicted to be affected by a fusion\u2010causing deletion. The existence of the mosaic deletion was subsequently confirmed clinically by an increased density copy number array and orthogonal methodologies<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>While mosaic mutations and deletions of <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">EXT<\/jats:styled-content>2<\/jats:italic> have been reported in the context of multiple osteochondromas, to our knowledge, this is the first time that transcriptomics technologies have been used to diagnose a patient via fusion transcript analysis in the congenital disease setting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.560","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T09:30:27Z","timestamp":1547199027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["RNA\u2010Seq detects a <i>SAMD12\u2010EXT1<\/i> fusion transcript and leads to the discovery of an <i>EXT1<\/i> deletion in a child with multiple osteochondromas"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9948-3799","authenticated-orcid":false,"given":"Gavin R.","family":"Oliver","sequence":"first","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester Minnesota"},{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-1275","authenticated-orcid":false,"given":"Patrick 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