{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:28:44Z","timestamp":1782790124394,"version":"3.54.5"},"reference-count":23,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Trichorhinophalangeal syndrome type I (TRPSI) is a rare disorder that causes distinctive ectodermal, facial, and skeletal features affecting the hair (tricho-), nose (rhino-), and fingers and toes (phalangeal) and is inherited in an autosomal dominant pattern. TRPSI is caused by loss of function variants in <jats:italic>TRPS1<\/jats:italic>, involved in the regulation of chondrocyte and perichondrium development. Pathogenic variants in <jats:italic>TRPS1<\/jats:italic> include missense mutations and deletions with variable breakpoints, with only a single instance of an intragenic duplication reported to date. Here we report an affected individual presenting with a classic TRPSI phenotype who is heterozygous for a de novo intragenic \u223c36.3-kbp duplication affecting exons 2\u20134 of <jats:italic>TRPS1<\/jats:italic>. Molecular analysis revealed the duplication to be in direct tandem orientation affecting the splicing of <jats:italic>TRPS1<\/jats:italic>. The aberrant transcripts are predicted to produce a truncated TRPS1 missing the nuclear localization signal and the GATA and IKAROS-like zinc-finger domains resulting in functional <jats:italic>TRPS1<\/jats:italic> haploinsufficiency. Our study identifies a novel intragenic tandem duplication of <jats:italic>TRPS1<\/jats:italic> and highlights the importance of molecular characterization of intragenic duplications.<\/jats:p>","DOI":"10.1101\/mcs.a004655","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T21:05:44Z","timestamp":1572383144000},"page":"a004655","source":"Crossref","is-referenced-by-count":8,"title":["An intragenic duplication of <i>TRPS1<\/i> leading to abnormal transcripts and causing trichorhinophalangeal syndrome type I"],"prefix":"10.1101","volume":"5","author":[{"given":"Cinthya J.","family":"Zepeda-Mendoza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot A.","family":"Cousin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Jenkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan T.","family":"Pittock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda B.","family":"Baughn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Klee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusica","family":"Babovic-Vuksanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"2021112506202853000_5.6.a004655.1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"2021112506202853000_5.6.a004655.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.10.025"},{"key":"2021112506202853000_5.6.a004655.3","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu078"},{"key":"2021112506202853000_5.6.a004655.4","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21438"},{"key":"2021112506202853000_5.6.a004655.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000327"},{"key":"2021112506202853000_5.6.a004655.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2017.11.009"},{"key":"2021112506202853000_5.6.a004655.7","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-224"},{"key":"2021112506202853000_5.6.a004655.8","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-4-r36"},{"key":"2021112506202853000_5.6.a004655.9","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320190110"},{"key":"2021112506202853000_5.6.a004655.10","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1107s32"},{"key":"2021112506202853000_5.6.a004655.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.037"},{"key":"2021112506202853000_5.6.a004655.12","unstructured":"Li H . 2013. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv e-prints."},{"key":"2021112506202853000_5.6.a004655.13","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"2021112506202853000_5.6.a004655.14","doi-asserted-by":"publisher","DOI":"10.1086\/316926"},{"key":"2021112506202853000_5.6.a004655.15","unstructured":"Maas S , Shaw A , Bikker H , Hennekam, RCM . 1993. Trichorhinophalangeal syndrome. In GeneReviews\u00ae (ed. Adam MP , Ardinger HH , Pagon RA , ). University of Washington, Seattle."},{"key":"2021112506202853000_5.6.a004655.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.03.002"},{"key":"2021112506202853000_5.6.a004655.17","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200"},{"key":"2021112506202853000_5.6.a004655.18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn125"},{"key":"2021112506202853000_5.6.a004655.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.12.017"},{"key":"2021112506202853000_5.6.a004655.20","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320240420"},{"key":"2021112506202853000_5.6.a004655.21","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1112s47"},{"key":"2021112506202853000_5.6.a004655.22","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.5"},{"key":"2021112506202853000_5.6.a004655.23","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs017"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a004655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T14:20:38Z","timestamp":1637850038000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a004655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,29]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,12,13]]},"published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1101\/mcs.a004655"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a004655","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,29]]}}}