{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:49:44Z","timestamp":1783648184151,"version":"3.55.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8]]},"abstract":"\nObjective<\/jats:title>\nSuccinate dehydrogenase B subunit (SDHB<\/jats:italic>) gene germline mutations predispose to pheochromocytomas, sympathetic paragangliomas, head and neck paragangliomas and non-paraganglionic tumors (e.g. renal cell carcinoma, gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study was to determine phenotypical characteristics of a large Dutch cohort of SDHB<\/jats:italic> germline mutation carriers and assess differences in clinical phenotypes related to specific SDHB<\/jats:italic> mutations.<\/jats:p>\n<\/jats:sec>\n\nDesign<\/jats:title>\nRetrospective descriptive study.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nRetrospective descriptive study in seven academic centers.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nWe included 194 SDHB<\/jats:italic> mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%) relatives. Mean age was 44.8\u2009\u00b1\u200916.0 years. Median duration of follow-up was 2.6 years (range: 0\u201336). Sixty persons (30.9%) carried the exon 3 deletion and 46 (23.7%) the c.423\u2009+\u20091G\u2009>\u2009A mutation. Fifty-four mutation carriers (27.8%) had one or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26 (13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%) developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic tumors. At study close, there were 111 (57.2%) unaffected mutation carriers. Statistical analyses showed no significant differences in the number and location of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas, nor in the occurrence of metastatic disease or other tumors between carriers of the two founder SDHB<\/jats:italic> mutations (exon 3 deletion vs c.423\u2009<\/jats:bold>+\u20091G\u2009>\u2009A).<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nIn this nationwide study of disease-affected and unaffected SDHB<\/jats:italic> mutation carriers, we observed a lower rate of metastatic disease and a relatively high number of head and neck paragangliomas compared with previously reported referral-based cohorts.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-17-0074","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T12:38:22Z","timestamp":1494506302000},"page":"115-125","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":44,"title":["The phenotype of SDHB germline mutation carriers: a nationwide study"],"prefix":"10.1093","volume":"177","author":[{"given":"Nicolasine D","family":"Niemeijer","sequence":"first","affiliation":[{"name":"1Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A","family":"Rijken","sequence":"additional","affiliation":[{"name":"2Department of Otorhinolaryngology\/Head and Neck Surgery, VU University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Eijkelenkamp","sequence":"additional","affiliation":[{"name":"3Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk N A","family":"van der Horst-Schrivers","sequence":"additional","affiliation":[{"name":"3Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel N","family":"Kerstens","sequence":"additional","affiliation":[{"name":"3Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carli M J","family":"Tops","sequence":"additional","affiliation":[{"name":"4Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"van Berkel","sequence":"additional","affiliation":[{"name":"5Division of Endocrinology, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri J L M","family":"Timmers","sequence":"additional","affiliation":[{"name":"5Division of Endocrinology, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henricus P M","family":"Kunst","sequence":"additional","affiliation":[{"name":"6Department of Otorhinolaryngology\/Head and Neck Surgery, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Ren\u00e9","family":"Leemans","sequence":"additional","affiliation":[{"name":"2Department of Otorhinolaryngology\/Head and Neck Surgery, VU University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H","family":"Bisschop","sequence":"additional","affiliation":[{"name":"7Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen M A","family":"Dreijerink","sequence":"additional","affiliation":[{"name":"8Department of Endocrine Oncology, University Medical Centre Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke F","family":"van Dooren","sequence":"additional","affiliation":[{"name":"9Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Bayley","sequence":"additional","affiliation":[{"name":"10Department of Human Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto M","family":"Pereira","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen C","family":"Jansen","sequence":"additional","affiliation":[{"name":"11Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik J","family":"Hes","sequence":"additional","affiliation":[{"name":"4Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik F","family":"Hensen","sequence":"additional","affiliation":[{"name":"2Department of Otorhinolaryngology\/Head and Neck Surgery, VU University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora P M","family":"Corssmit","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref171","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/humu.21136","article-title":"Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD","volume":"31","year":"2010","journal-title":"Human Mutation"},{"key":"ref201","doi-asserted-by":"publisher","first-page":"201118","DOI":"10.1530\/ERC-11-0170","article-title":"WelanderJSoderkvistPGimmO and clinical characteristics of hereditary pheochromocytomas and paragangliomas - Related","journal-title":"Genetics Endocrine Cancer"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/PAT.0b013e3283539932","article-title":"Succinate dehydrogenase (SDH) and mitochondrial driven 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