{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:44:02Z","timestamp":1783644242270,"version":"3.55.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:p>Context and Objective: Germline mutations of the genes SDHB, SDHC, and SDHD predispose to paraganglioma syndromes. Mutation-specific counseling, risk assessment, and management recommendations ideally should be performed. Here, we provide data for a single common mutation of the SDHD gene.<\/jats:p>\n               <jats:p>Methods: The European-American Pheochromocytoma-Paraganglioma Registry served as the source for unrelated index cases affected by pheochromocytoma or paraganglioma. Patients with the SDHD c.33 C\u2192A (p.Cys11X) germline mutations were reinvestigated by whole-body magnetic resonance imaging and 24-h urinary catecholamine assay. First-degree relatives underwent genetic testing and those testing positive had same clinical investigations. Microsatellite analyses were used to test the hypothesis that all index cases were related and the mutation is a founding one.<\/jats:p>\n               <jats:p>Results: Sixteen index cases with the mutation SDHD p.Cys11X are registered. After testing their relatives, there were a total of 25 mutation carriers. We excluded seven subjects who inherited the mutation from the mother because of maternal imprinting. Thus, 18 mutation carriers were clinically affected. Among these 16 (89%) had head and neck paragangliomas, six (33%) thoracic tumors, six (33%) extraadrenal retroperitoneal, and five (28%) intraadrenal. Of note, 16 (89%) had multiple tumors at first diagnosis, and one (5%) had signs of malignancy during follow-up. Overall penetrance was 100% at age 54. Haplotype analyses revealed evidence for a founder effect.<\/jats:p>\n               <jats:p>Conclusions: The SDHD p.Cys11X mutation is a founding mutation associated with a high penetrance for paraganglial tumors of the skull base, neck, thorax, and retroperitoneum in the first four decades of life and, rarely, with malignancy.<\/jats:p>","DOI":"10.1210\/jc.2008-1290","type":"journal-article","created":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T02:53:39Z","timestamp":1222829619000},"page":"4818-4825","source":"Crossref","is-referenced-by-count":23,"title":["Impact of Screening Kindreds for SDHD p.Cys11X as a Common Mutation Associated with Paraganglioma Syndrome Type 1"],"prefix":"10.1210","volume":"93","author":[{"given":"Mariola","family":"Pe\u0328czkowska","sequence":"first","affiliation":[{"name":"Department of Hypertension (M.P., A.Ku., A.P., A.J.), Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Erlic","sequence":"additional","affiliation":[{"name":"Departments of Nephrology and Hypertension (Z.E., M.S., H.P.H.N.) Albert-Ludwigs-University, D-79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Laboratory Medicine (M.M.H.), Albert-Ludwigs-University, D-79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Furmanek","sequence":"additional","affiliation":[{"name":"Department of Radiology and Diagnostic Imaging at the Medical Center for Postgraduate Education (M.F., J.C.), 02-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"C\u0301wik\u0142a","sequence":"additional","affiliation":[{"name":"Department of Radiology and Diagnostic Imaging at the Medical Center for Postgraduate Education (M.F., J.C.), 02-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Kubaszek","sequence":"additional","affiliation":[{"name":"Department of Hypertension (M.P., A.Ku., A.P., A.J.), Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Prejbisz","sequence":"additional","affiliation":[{"name":"Department of Hypertension (M.P., A.Ku., A.P., A.J.), Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Szutkowski","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Cancer (Z.S., A.Ka.), Sk\u0142odowska-Curie Memorial Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Kawecki","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Cancer (Z.S., A.Ka.), Sk\u0142odowska-Curie Memorial Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Chojnowski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (K.C.), Medical University of Warsaw, 02-091Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lewczuk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (A.L.), Endocrinology and Haemostatic Disorders, Medical University of Gdansk, 80-952 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczys\u0142aw","family":"Litwin","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension (M.L.), the Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witold","family":"Szyfter","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology (W.S.), Karol Marcinkowski University of Medical Sciences, 61-701, Poznan\u0301, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A.","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nuclear Medicine (M.A.W.), University of Basel, CH-4051 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Departments of Nephrology and Hypertension (Z.E., M.S., H.P.H.N.) Albert-Ludwigs-University, D-79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute (C.E.), Lerner Research Institute and Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Januszewicz","sequence":"additional","affiliation":[{"name":"Department of Hypertension (M.P., A.Ku., A.P., A.J.), Institute of Cardiology, 04-628 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut P. H.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Departments of Nephrology and Hypertension (Z.E., M.S., H.P.H.N.) Albert-Ludwigs-University, D-79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613431755900_R1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1126\/science.287.5454.848","article-title":"Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.","volume":"287","author":"Baysal","year":"2000","journal-title":"Science"},{"key":"2020071613431755900_R2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/81551","article-title":"Mutations in SDHC cause autosomal dominant paraganglioma, type 3.","volume":"26","author":"Niemann","year":"2000","journal-title":"Nat Genet"},{"key":"2020071613431755900_R3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1086\/321282","article-title":"Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.","volume":"69","author":"Astuti","year":"2001","journal-title":"Am J Hum Genet"},{"key":"2020071613431755900_R4","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/S0140-6736(89)91908-9","article-title":"Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory.","volume":"2","author":"van der Mey","year":"1989","journal-title":"Lancet"},{"key":"2020071613431755900_R5","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1210\/jc.2007-1989","article-title":"Paraganglioma after maternal transmission of a succinate dehydrogenase gene mutation.","volume":"93","author":"Pigny","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613431755900_R6","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1210\/jc.2008-0569","article-title":"Maternal transmission of symptomatic disease with SDHD mutation: fact or fiction?","volume":"93","author":"Neumann","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613431755900_R7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/BF00225075","article-title":"Fine mapping of a putatively imprinted gene for familial non-chromaffin paragangliomas to chromosome 11q13.1: evidence for genetic heterogeneity.","volume":"95","author":"Mariman","year":"1995","journal-title":"Hum Genet"},{"key":"2020071613431755900_R8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1741-7007-5-12","article-title":"Sequence variation in human succinate dehydrogenase genes: evidence for long-term balancing selection on SDHA","volume":"5","author":"Baysal","year":"2007","journal-title":"BMC Biol"},{"key":"2020071613431755900_R9","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1056\/NEJMoa020152","article-title":"Germ-line mutations in nonsyndromic pheochromocytoma.","volume":"346","author":"Neumann","year":"2002","journal-title":"N Engl J Med"},{"key":"2020071613431755900_R10","first-page":"943","article-title":"Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.","volume":"292","author":"Neumann","year":"2004","journal-title":"JAMA [Erratum (2004) 292:1686]"},{"key":"2020071613431755900_R11","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1001\/jama.294.16.2057","article-title":"Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene.","volume":"294","author":"Schiavi","year":"2005","journal-title":"JAMA"},{"key":"2020071613431755900_R12","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1136\/jmg.2003.011551","article-title":"The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features","volume":"41","author":"Badenhop","year":"2004","journal-title":"J Med Genet"},{"key":"2020071613431755900_R13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1136\/jmg.39.3.178","article-title":"Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.","volume":"39","author":"Baysal","year":"2002","journal-title":"J Med Genet"},{"key":"2020071613431755900_R14","first-page":"5615","article-title":"Mutations in the SDHB gene are associated with extra-adrenal and\/or malignant phaeochromocytomas.","volume":"63","author":"Gimenez-Roqueplo","year":"2003","journal-title":"Cancer Res"},{"key":"2020071613431755900_R15","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1046\/j.1365-2265.2003.01914.x","article-title":"Genetic analysis of mitochondrial complex II subunits SDHD, SDHB and SDHC in paraganglioma and phaeochromocytoma susceptibility.","volume":"59","author":"Astuti","year":"2003","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613431755900_R16","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1210\/jc.2006-2315","article-title":"Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas.","volume":"92","author":"Timmers","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613431755900_R17","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1136\/jmg.2007.051045","article-title":"Genetic screening for pheochromocytoma: should SDHC gene analysis be included?","volume":"44","author":"Mannelli","year":"2007","journal-title":"J Med Genet"},{"key":"2020071613431755900_R18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/ncpendmet0726","article-title":"Extra-adrenal and adrenal pheochromocytomas associated with a germline SDHC mutation.","volume":"4","author":"Peczkowska","year":"2008","journal-title":"Nat Clin Pract 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Metab"},{"key":"2020071613431755900_R24","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s00439-003-0969-6","article-title":"Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect.","volume":"113","author":"Astrom","year":"2003","journal-title":"Hum Genet"},{"key":"2020071613431755900_R25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0005-2728(97)00019-4","article-title":"Succinate: quinone oxidoreductases. Variations on a conserved theme.","volume":"1320","author":"Hagerhall","year":"1997","journal-title":"Biochim Biophys Acta"},{"key":"2020071613431755900_R26","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1111\/j.1432-1033.1992.tb16892.x","article-title":"The distribution of charged amino acids in mitochondrial inner-membrane proteins suggests different modes of membrane integration for nuclearly and mitochondrially encoded proteins.","volume":"205","author":"Gavel","year":"1992","journal-title":"Eur J Biochem"},{"key":"2020071613431755900_R27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1471-2350-6-39","article-title":"The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency","volume":"6","author":"Bayley","year":"2005","journal-title":"BMC Med Genet"},{"key":"2020071613431755900_R28","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1086\/324413","article-title":"The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway.","volume":"69","author":"Gimenez-Roqueplo","year":"2001","journal-title":"Am J Hum Genet"},{"key":"2020071613431755900_R29","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/29331","article-title":"A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes.","volume":"394","author":"Ishii","year":"1998","journal-title":"Nature"},{"key":"2020071613431755900_R30","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/j.1365-2265.2007.03086.x","article-title":"Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.","volume":"68","author":"Timmers","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613431755900_R31","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1210\/jc.2006-1993","article-title":"Malignant paragangliomas associated with mutations in the succinate dehydrogenase D gene.","volume":"92","author":"Havekes","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613431755900_R32","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/hed.20746","article-title":"Malignant paraganglioma caused by a novel germline mutation of the succinate dehydrogenase D-gene-A case report.","volume":"30","author":"Papaspyrou","year":"2008","journal-title":"Head Neck"},{"key":"2020071613431755900_R33","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.1210\/jc.2002-021069","article-title":"The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors.","volume":"87","author":"Koch","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613431755900_R34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/sj.ejhg.5201904","article-title":"Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD.","volume":"16","author":"Pasini","year":"2008","journal-title":"Eur J Hum Genet"},{"key":"2020071613431755900_R35","author":"Young Jr","year":"2008"},{"key":"2020071613431755900_R36","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/gcc.1144","article-title":"Nearly all hereditary paragangliomas in The Netherlands are caused by two founder mutations in the SDHD gene.","volume":"31","author":"Taschner","year":"2001","journal-title":"Genes Chromosomes Cancer"},{"key":"2020071613431755900_R37","first-page":"2061","article-title":"Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma.","volume":"8","author":"Dannenberg","year":"2002","journal-title":"Clin Cancer Res"},{"key":"2020071613431755900_R38","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1136\/jmg.2004.030353","article-title":"Phenotype variability of neural crest derived tumours in six Italian families segregating the same founder SDHD mutation Q109X","volume":"42","author":"Simi","year":"2005","journal-title":"J Med Genet"},{"key":"2020071613431755900_R39","first-page":"S327","article-title":"A founder mutation in the SDHD gene as the cause of the high prevalence of head and neck paraganglioma in Trentino, Italy","volume":"24","author":"Schiavi","year":"2006","journal-title":"J Hypertens"},{"key":"2020071613431755900_R40","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/01.pas.0000158987.07907.7e","article-title":"Mutation analysis of the SDHD gene in four kindreds with familial paraganglioma: description of one novel germline mutation.","volume":"14","author":"Velasco","year":"2005","journal-title":"Diagn Mol Pathol"}],"container-title":["The Journal of Clinical Endocrinology &amp; 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