{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:15:36Z","timestamp":1774685736052,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T00:00:00Z","timestamp":1358899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple osteochondromas (MO) is a syndrome in which benign cartilage\u2010capped neoplasms develop at the surface of the long bones. Most cases are caused by exonic changes in <jats:italic>EXT1<\/jats:italic> or <jats:italic>EXT2<\/jats:italic>, but 15% are negative for these changes. Here we report for the first time a family of MO patients with germline genomic alterations at the <jats:italic>EXT1<\/jats:italic> locus without detectable mutations or copy number alterations of <jats:italic>EXT<\/jats:italic> exonic sequences. Array\u2010CGH showed an 80.7 kb deletion of Intron 1 of <jats:italic>EXT1<\/jats:italic> and a 68.9 kb duplication proximal of <jats:italic>EXT1<\/jats:italic>. We identified a breakpoint between the distal end of the duplicated region and a sequence distal of the deleted region in the first intron. This breakpoint was absent in non\u2010affected family members. The configuration of the breakpoint indicates a direct insertion of the duplicated region into the deletion. However, no other breakpoint was found, which suggests a more complex genomic rearrangement has occurred within the duplicated region. Our results reveal intronic deletion and duplication as a new causative mechanism for MO not detected by conventional diagnostic methods. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22041","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T12:34:58Z","timestamp":1358944498000},"page":"431-436","source":"Crossref","is-referenced-by-count":15,"title":["Intronic deletion and duplication proximal of the <i>EXT1<\/i> gene: A novel causative mechanism for multiple osteochondromas"],"prefix":"10.1002","volume":"52","author":[{"given":"Cathelijn J. F.","family":"Waaijer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel G. T.","family":"Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christianne M. A.","family":"Reijnders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dani\u00eblle","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"John Ham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith V. M. G.","family":"Bov\u00e9e","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e1roly","family":"Szuhai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-137"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-572"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/321278"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.212"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.309"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2840"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2008.070086"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21123"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-12-85"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21471"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100296"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21423"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201343"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20054"},{"key":"e_1_2_6_16_1","first-page":"234","volume-title":"World Health Organization Classification of Tumours. Pathology and Genetics","author":"WHO","year":"2002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1547"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2008.12.004"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22041","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:47:51Z","timestamp":1700614071000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,23]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1002\/gcc.22041"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22041","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,23]]}}}