{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:01:07Z","timestamp":1774645267324,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,12,7]],"date-time":"2011-12-07T00:00:00Z","timestamp":1323216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Germline mutations in the <jats:italic>HRPT2<\/jats:italic> gene are associated with the hereditary hyperparathyroidism\u2010jaw tumour syndrome (HPT\u2010JT) and a subset of familial isolated hyperparathyroidism (FIHP). Somatic <jats:italic>HRPT2<\/jats:italic> mutations are detected in sporadic parathyroid carcinomas and less frequently in cystic adenomas. The purpose of this study was to investigate the underlying <jats:italic>HRPT2<\/jats:italic> defect in a young patient with symptomatic hyperparathyroidism due to an apparently sporadic parathyroid adenoma with cystic features.<\/jats:p><jats:p><jats:bold>Design and Methods\u2002<\/jats:bold>  <jats:italic>HRPT2<\/jats:italic> mutations in the patient\u2019s genomic and parathyroid tumour DNA were screened by PCR\u2010based sequencing. Tumour loss of heterozygosity (LOH) at the <jats:italic>HRPT2 locus<\/jats:italic> was assessed with microsatellite markers. A large germline <jats:italic>HRPT2<\/jats:italic> deletion was investigated by real\u2010time quantitative PCR analysis (qPCR). Genomic DNA losses were also appraised by chromosomal comparative genomic hybridization (cCGH).<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> No germline <jats:italic>HRPT2<\/jats:italic> point mutation was detected by direct sequencing. A novel hemizygous <jats:italic>HRPT2<\/jats:italic> somatic mutation (c.32delA) was identified in the tumour. Apparent constitutional homozygosity for <jats:italic>HRPT2<\/jats:italic> flanking microsatellite markers, and absence of LOH at a distal marker, suggested a large germline deletion. Gene dose mapping by qPCR unveiled a <jats:italic>de novo<\/jats:italic> deletion of the whole <jats:italic>HRPT2<\/jats:italic> gene and adjacent <jats:italic>loci<\/jats:italic> (&lt;9\u00b73\u2003Mb in size). cCGH confirmed germline DNA loss involving the <jats:italic>HRPT2 locus<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> We report the first large germline deletion of the <jats:italic>HRPT2<\/jats:italic> gene, which was not detectable by conventional PCR\u2010based sequencing methods. This finding emphasizes that qPCR should be implemented in <jats:italic>HRPT2<\/jats:italic> molecular analysis, which may improve genetic assessment and clinical management of patients with FIHP and HPT\u2010JT.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2011.04184.x","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T13:40:07Z","timestamp":1311687607000},"page":"33-38","source":"Crossref","is-referenced-by-count":36,"title":["Identification of the first germline <i>HRPT2<\/i> whole\u2010gene deletion in a patient with primary hyperparathyroidism"],"prefix":"10.1111","volume":"76","author":[{"given":"Rita","family":"Domingues","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rute Alexandra","family":"Tomaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmo","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Nunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Jo\u00e3o","family":"Bugalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branca Maria","family":"Cavaco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,12,7]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1048"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/94.4.213"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031016"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2004.01421.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21188"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.12.5052-5060.2005"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp991"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0066"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.9.657"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031237"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0294"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-011-9151-1"},{"key":"e_1_2_7_14_2","first-page":"128","volume-title":"World Health Organization Classification of Tumours. 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