{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:26:39Z","timestamp":1771028799884,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T00:00:00Z","timestamp":1398988800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the <jats:italic>TRPS1<\/jats:italic> gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the <jats:italic>TRPS1<\/jats:italic> gene, have been reported. A deregulated expression of <jats:italic>TRPS1<\/jats:italic> has been hypothesised as cause of the TRPS phenotype of these patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) <jats:italic>de novo<\/jats:italic> balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting <jats:italic>TRPS1<\/jats:italic> or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of <jats:italic>TRPS1<\/jats:italic>, and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA <jats:italic>LINC00536<\/jats:italic>, at approximately 300\u00a0kb from the <jats:italic>TRPS1<\/jats:italic> 5\u2019 end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325\u00a0kb from the <jats:italic>TRPS1<\/jats:italic> promoter.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We suggest that the disruption of the genomic architecture of <jats:italic>cis<\/jats:italic> regulatory elements downstream the <jats:italic>TRPS1<\/jats:italic> 5\u2032 region, combined with the translocation of a novel enhancer element nearby <jats:italic>TRPS1<\/jats:italic>, might be the pathogenetic mechanism underpinning the proband\u2019s phenotype. The clinical and genetic characterisation of the present subject allowed us to make a genetic diagnosis in the context of a known syndrome, contributing to a better comprehension of the complex transcriptional regulation of <jats:italic>TRPS1<\/jats:italic> and TRPS ethiopathogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-15-52","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T11:01:24Z","timestamp":1399028484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene"],"prefix":"10.1186","volume":"15","author":[{"given":"Milena","family":"Crippa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Bestetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Perotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Castronovo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Tabano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Picinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Grassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Larizza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela Ida","family":"Pincelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Palma","family":"Finelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,5,2]]},"reference":[{"key":"1195_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/71717","volume":"24","author":"P Momeni","year":"2000","unstructured":"Momeni P, Gl\u00f6ckner G, Schmidt O, von Holtum D, Albrecht B, Gillessen-Kaesbach G, Hennekam R, Meinecke P, Zabel B, Rosenthal A, Horsthemke B, L\u00fcdecke HJ: Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I. 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