{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:27:56Z","timestamp":1789442876100,"version":"build-2803163510"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:p>\n                    Mutations in the tumour suppressor\n                    <jats:italic>HRPT2<\/jats:italic>\n                    occur in patients with parathyroid carcinoma, kidney tumours and Hyperparathyroidism\u2013Jaw Tumour syndrome. Disruption of exonic splicing through mutation of donor\/acceptor splice sites or exonic splice enhancer (ESE) sites leads to loss of function of a number of major tumour suppressors including\n                    <jats:italic>BRCA1<\/jats:italic>\n                    ,\n                    <jats:italic>APC<\/jats:italic>\n                    and\n                    <jats:italic>MLH1<\/jats:italic>\n                    . Given that the effect of\n                    <jats:italic>HRPT2<\/jats:italic>\n                    mutations on splicing has not been widely studied, we used an\n                    <jats:italic>in vitro<\/jats:italic>\n                    splicing assay to determine whether 17\n                    <jats:italic>HRPT2<\/jats:italic>\n                    mutations located in hot-spot and other exons predicted to disrupt ESE consensus sites led to aberrant splicing. Using two independent web-based prediction programs, the majority of these mutations were predicted to disrupt ESE consensus sites; however, aberrant splicing of\n                    <jats:italic>HRPT2<\/jats:italic>\n                    transcripts was not observed. Canonical donor or acceptor splice site mutations were also investigated using this splicing assay and transcripts assessed from tumour tissue. Splice site mutations were shown to lead to either exon skipping or retention of intronic sequences through the use of cryptic splice sites comprised of non-classical splicing signals. Aberrant splicing caused by disruption of ESE sites does not appear to have a major role in\n                    <jats:italic>HRPT2<\/jats:italic>\n                    -associated disease; however, premature truncation of parafibromin as the result of canonical donor or acceptor splice site mutations is associated with pathogenicity. Functional splicing assays must be undertaken in order to confirm web-based software predictions of the modification of putative ESE sites by disease-associated mutations.\n                  <\/jats:p>","DOI":"10.1677\/joe-09-0038","type":"journal-article","created":{"date-parts":[[2009,3,30]],"date-time":"2009-03-30T20:34:18Z","timestamp":1238445258000},"page":"387-396","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":9,"title":["The effect of disease-associated HRPT2 mutations on splicing"],"prefix":"10.1530","volume":"201","author":[{"given":"Michael A","family":"Hahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"McDonnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/201\/3\/387.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/201\/3\/387.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:41Z","timestamp":1784555681000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/201\/3\/387-396\/21808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,30]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1677\/joe-09-0038","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,30]]}}}