{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T15:58:02Z","timestamp":1708617482744},"reference-count":17,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T00:00:00Z","timestamp":1427673600000},"content-version":"unspecified","delay-in-days":88,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genet. Res."],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Background: Paraganglioma syndrome type 1 (PGL1) is a rare autosomal dominant syndrome associated with multiple, overwhelmingly benign, pheochromocytomas and paragangliomas, attributed to <jats:italic>SDHD<\/jats:italic> gene mutations. Objective: Clinically and molecularly characterize a family with uncommon malignant phenotype of paragangliomas attributed to two seemingly pathogenic <jats:italic>SDHD<\/jats:italic> germline mutations. Materials &amp; methods: The proband presented with large bilateral carotid body tumours and family history of cervical masses in his five siblings. All family members underwent clinical examination, imaging studies (<jats:sup>18<\/jats:sup>F-FDG PET\/CT) and genotyping of relevant genes. The proband was diagnosed with locally advanced paraganglioma; his hypertensive, otherwise asymptomatic father, had locally advanced pheochromocytoma and his three siblings showed multiple head and neck masses, confirmed to be paragangliomas with local metastasis. All affected patients carried two germline mutations in the <jats:italic>SDHD<\/jats:italic> gene; a previously reported nonsense mutation in exon 1 (p.Trp5X) and a novel missense mutation in exon 2 (p.Pro53Leu), highly deleterious by <jats:italic>in silico<\/jats:italic> analysis. Allelic loss at the <jats:italic>SDHD<\/jats:italic> locus was not shown for any of the analysed tumours. Conclusions: This is a rare case of malignant PGL1 with seemingly double pathogenic mutations in the <jats:italic>SDHD<\/jats:italic> gene, highlighting the possibility that the presence of both mutations is associated with the more aggressive phenotype.<\/jats:p>","DOI":"10.1017\/s0016672315000063","type":"journal-article","created":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T06:52:27Z","timestamp":1427698347000},"source":"Crossref","is-referenced-by-count":4,"title":["Malignant phenotype and two <i>SDHD<\/i> mutations in a family with paraganglioma syndrome type 1"],"prefix":"10.1155","volume":"97","author":[{"given":"FRANCIELE B.","family":"LEIDENZ","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LUCIANA","family":"BASTOS-RODRIGUES","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MARCELO","family":"OLIVEIRA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MARCELO","family":"MAMEDE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MARTA","family":"SARQUIS","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EITAN","family":"FRIEDMAN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LUIZ","family":"DE MARCO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"98","published-online":{"date-parts":[[2015,3,30]]},"reference":[{"key":"S0016672315000063_ref7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1498"},{"key":"S0016672315000063_ref12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.8.943"},{"key":"S0016672315000063_ref9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"S0016672315000063_ref6","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.19.5444"},{"key":"S0016672315000063_ref14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1989"},{"key":"S0016672315000063_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.04.001"},{"key":"S0016672315000063_ref8","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/794187"},{"key":"S0016672315000063_ref4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.26.3001"},{"key":"S0016672315000063_ref3","first-page":"108","article-title":"Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity","volume":"14","author":"Dahia","year":"2014","journal-title":"Nature Reviews"},{"key":"S0016672315000063_ref11","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0569"},{"key":"S0016672315000063_ref10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020152"},{"key":"S0016672315000063_ref13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2009.02111.x"},{"key":"S0016672315000063_ref15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1963"},{"key":"S0016672315000063_ref16","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0170"},{"key":"S0016672315000063_ref2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.011551"},{"key":"S0016672315000063_ref17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1244"},{"key":"S0016672315000063_ref1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.1484"}],"container-title":["Genetics Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0016672315000063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T22:46:09Z","timestamp":1609454769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0016672315000063\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":17,"alternative-id":["S0016672315000063"],"URL":"https:\/\/doi.org\/10.1017\/s0016672315000063","relation":{},"ISSN":["0016-6723","1469-5073"],"issn-type":[{"value":"0016-6723","type":"print"},{"value":"1469-5073","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015]]},"article-number":"e3"}}