{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:29:20Z","timestamp":1790270960095,"version":"4.1.0"},"reference-count":26,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Paraganglioma (PGL) has the highest degree of heritability among human neoplasms. Current clinical understanding of germline SDHA mutation carriers is limited.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To estimate the contribution of SDHA mutations in PGL and to assess clinical manifestations and age-related penetrance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Nationwide retrospective cohort study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Tertiary referral centers in the Netherlands (multicenter).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Germline SDHA analysis was performed in 393 patients with genetically unexplained PGL. Subsequently, 30 index SDHA mutation carriers and 56 nonindex carriers were studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>SDHA mutation detection yield, clinical manifestations, and SDHA-related disease penetrance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Pathogenic germline SDHA variants were identified in 30 of the 393 referred patients with PGL (7.6%), who had head and neck PGL (21 of 174 [12%]), pheochromocytoma (4 of 191 [2%]), or sympathetic PGL (5 of 28 [18%]). The median age at diagnosis was 43 years (range, 17 to 81 years) in index SDHA mutation carriers compared with 52 years (range, 7 to 90 years) in nonmutation carriers (P = 0.002). The estimated penetrance of any SDHA-related manifestation was 10% at age 70 years (95% confidence interval, 0% to 21%) in nonindex mutation carriers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Germline SDHA mutations are relatively common (7.6%) in patients with genetically unexplained PGL. Most index patients presented with apparently sporadic PGL. In this SDHA series, the largest assembled so far, we found the lowest penetrance of all major PGL predisposition genes. This suggests that recommendations for genetic counseling of at-risk relatives and stringency of surveillance for SDHA mutation carriers might need to be reassessed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2017-01762","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T19:06:08Z","timestamp":1511291168000},"page":"438-445","source":"Crossref","is-referenced-by-count":75,"title":["Clinical Aspects of SDHA-Related Pheochromocytoma and Paraganglioma: A Nationwide Study"],"prefix":"10.1210","volume":"103","author":[{"given":"Karin","family":"van der Tuin","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen R","family":"Mensenkamp","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carli M J","family":"Tops","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Laboratory for Diagnostic Genetic Analysis, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora P M","family":"Corssmit","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winand N","family":"Dinjens","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk N","family":"van de Horst-Schrivers","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen C","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam M","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henricus P M","family":"Kunst","sequence":"additional","affiliation":[{"name":"Department Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benno","family":"Kusters","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Leter","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Morreau","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette M P","family":"van Nesselrooij","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier A","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"Spruijt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik J","family":"Hes","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri J L M","family":"Timmers","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"issue":"6","key":"2020071622164978900_B1","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1210\/jc.2014-1498","article-title":"Pheochromocytoma and paraganglioma: an Endocrine Society clinical practice guideline","volume":"99","author":"Lenders","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2020071622164978900_B2","doi-asserted-by":"crossref","first-page":"T91","DOI":"10.1530\/ERC-15-0268","article-title":"15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1-5","volume":"22","author":"Benn","year":"2015","journal-title":"Endocr Relat Cancer"},{"issue":"5","key":"2020071622164978900_B3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1210\/er.2014-1026","article-title":"Current approaches and recent developments in the management of head and neck 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