{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSDHD encodes one of the four essential subunits of succinate dehydrogenase (SDH), an enzyme complex that uniquely links the tricarboxylic acid cycle with the mitochondrial respiratory chain. SDHD’s normal function is critical for catalyzing the oxidation of succinate to fumarate and supporting electron transport. Inherited inactivating mutations in SDHD act as a tumor‐suppressor defect that predisposes carriers to a spectrum of neuroendocrine neoplasms—including pheochromocytomas, head and neck paragangliomas, and related glomus tumors—and display unusual inheritance patterns involving parent‐of‐origin effects. Several genetic studies have demonstrated that SDHD mutations constitute part of a panel of susceptibility genes routinely screened in patients with both familial and apparently sporadic endocrine tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the biochemical level, loss of SDHD function compromises the integrity of mitochondrial complex II, leading to a selective loss of its enzymatic activity. This deficiency results in succinate accumulation, which in turn inhibits α‐ketoglutarate–dependent dioxygenases and stabilizes hypoxia inducible factors even under normal oxygen conditions—a state known as pseudo‐hypoxia. The ensuing metabolic reprogramming not only triggers overexpression of angiogenic factors but also diminishes cellular metabolic plasticity, as confirmed through studies using cellular models and investigations of complex II deficiencies in patient tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, the detection of SDHD mutations bears significant implications for the management of patients with neuroendocrine tumors. Routine genetic testing—including immunohistochemical screening for SDH deficiency—has proven valuable in identifying individuals at risk for multifocal and aggressive forms of pheochromocytoma, paraganglioma, and even tumors outside the classical spectrum such as gastrointestinal stromal tumors and certain renal cancers. As a result, genotype–phenotype correlations are increasingly incorporated into surveillance protocols and therapeutic decision making, thereby facilitating tailored counseling and management for mutation carriers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A P Gimenez-Roqueplo, J Favier, P Rustin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/324413"}], "href": "https://doi.org/10.1086/324413"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11605159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11605159"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "B E Baysal, J E Willett-Brozick, E C Lawrence, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.39.3.178"}], "href": "https://doi.org/10.1136/jmg.39.3.178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11897817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11897817"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hartmut P H Neumann, Birke Bausch, Sarah R McWhinney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germ-line mutations in nonsyndromic pheochromocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa020152"}], "href": "https://doi.org/10.1056/NEJMoa020152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12000816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12000816"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Soili Kytölä, Brita Nord, Elisabeth Edström Elder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.10081"}], "href": "https://doi.org/10.1002/gcc.10081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12007193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12007193"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alberto Cascon, Sergio Ruiz-Llorente, Arancha Cebrian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ejhg.5200829"}], "href": "https://doi.org/10.1038/sj.ejhg.5200829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12111639"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12111639"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hilde Dannenberg, Winand N M Dinjens, Mustaffa Abbou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12114404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12114404"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Charis Eng, Maija Kiuru, Magali J Fernandez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for mitochondrial enzymes in inherited neoplasia and beyond."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Cancer (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrc1013"}], "href": "https://doi.org/10.1038/nrc1013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12612654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12612654"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wataru Habano, Tamotsu Sugai, Shin-Ichi Nakamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced expression and loss of heterozygosity of the SDHD gene in colorectal and gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12883710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12883710"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hartmut P H Neumann, Christian Pawlu, Mariola Peczkowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jama.292.8.943"}], "href": "https://doi.org/10.1001/jama.292.8.943"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15328326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15328326"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Laurence Amar, Jérôme Bertherat, Eric Baudin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic testing in pheochromocytoma or functional paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2005.03.1484"}], "href": "https://doi.org/10.1200/JCO.2005.03.1484"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16314641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16314641"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "B Havekes, E P M Corssmit, J C Jansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Malignant paragangliomas associated with mutations in the succinate dehydrogenase D gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2006-1993"}], "href": "https://doi.org/10.1210/jc.2006-1993"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17227803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17227803"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "T P C Martin, R M Irving, E R Maher "}, {"type": "b", "children": [{"type": "t", "text": "The genetics of paragangliomas: a review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Otolaryngol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2273.2007.01378.x"}], "href": "https://doi.org/10.1111/j.1365-2273.2007.01378.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17298303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17298303"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Carsten Christof Boedeker, Hartmut P H Neumann, Wolfgang Maier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Malignant head and neck paragangliomas in SDHB mutation carriers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Otolaryngol Head Neck Surg (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.otohns.2007.01.015"}], "href": "https://doi.org/10.1016/j.otohns.2007.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17599579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17599579"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Pascal Pigny, Audrey Vincent, Catherine Cardot Bauters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paraganglioma after maternal transmission of a succinate dehydrogenase gene mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2007-1989"}], "href": "https://doi.org/10.1210/jc.2007-1989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18211978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18211978"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Ying Ni, Kevin M Zbuk, Tammy Sadler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.07.011"}], "href": "https://doi.org/10.1016/j.ajhg.2008.07.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18678321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18678321"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Christopher Ricketts, Emma R Woodward, Pip Killick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline SDHB mutations and familial renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djn254"}], "href": "https://doi.org/10.1093/jnci/djn254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18728283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18728283"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Henri J L M Timmers, Karel Pacak, Thanh T Huynh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biochemically silent abdominal paragangliomas in patients with mutations in the succinate dehydrogenase subunit B gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2008-1093"}], "href": "https://doi.org/10.1210/jc.2008-1093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18840642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18840642"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Massimo Mannelli, Maurizio Castellano, Francesca Schiavi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2008-2419"}], "href": "https://doi.org/10.1210/jc.2008-2419"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19223516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19223516"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Alberto Cascón, Guillermo Pita, Nelly Burnichon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetics of pheochromocytoma and paraganglioma in Spanish patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2008-2756"}], "href": "https://doi.org/10.1210/jc.2008-2756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19258401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19258401"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "A Cascón, E López-Jiménez, I Landa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rationalization of genetic testing in patients with apparently sporadic pheochromocytoma/paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Horm Metab Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0029-1202814"}], "href": "https://doi.org/10.1055/s-0029-1202814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19343621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19343621"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Mary A Selak, Raul V Durán, Eyal Gottlieb "}, {"type": "b", "children": [{"type": "t", "text": "Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2006.05.015"}], "href": "https://doi.org/10.1016/j.bbabio.2006.05.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16797480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16797480"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Charlotte L Alston, Camilla Ceccatelli Berti, Emma L Blakely, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-015-1568-z"}], "href": "https://doi.org/10.1007/s00439-015-1568-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26008905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26008905"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "J Pfleger, M He, M Abdellatif "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2015.202"}], "href": "https://doi.org/10.1038/cddis.2015.202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26225774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26225774"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Charlotte Lussey-Lepoutre, Alexandre Bellucci, Aurélie Morin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In Vivo Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of SDHx Mutations in Paraganglioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-15-1576"}], "href": "https://doi.org/10.1158/1078-0432.CCR-15-1576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26490314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26490314"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Charlotte Lussey-Lepoutre, Kate E R Hollinshead, Christian Ludwig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms9784"}], "href": "https://doi.org/10.1038/ncomms9784"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26522426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26522426"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Millie Fullerton, Robert McFarland, Robert W Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The genetic basis of isolated mitochondrial complex II deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2020.09.009"}], "href": "https://doi.org/10.1016/j.ymgme.2020.09.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33162331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33162331"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Barbara Pasini, Sarah R McWhinney, Thalia Bei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ejhg.5201904"}], "href": "https://doi.org/10.1038/sj.ejhg.5201904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17667967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17667967"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Christopher J Ricketts, Julia R Forman, Eleanor Rattenberry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21136"}], "href": "https://doi.org/10.1002/humu.21136"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19802898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19802898"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Zoran Erlic, Lisa Rybicki, Mariola Peczkowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-09-1237"}], "href": "https://doi.org/10.1158/1078-0432.CCR-09-1237"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19825962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19825962"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Anthony J Gill, Diana E Benn, Angela Chou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2009.12.005"}], "href": "https://doi.org/10.1016/j.humpath.2009.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20236688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20236688"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "E F Hensen, M D Siemers, J C Jansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SDHD are the major determinants of the clinical characteristics of Dutch head and neck paraganglioma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2011.04097.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2011.04097.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21561462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21561462"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Berdine L Heesterman, Jean Pierre Bayley, Carli M Tops, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High prevalence of occult paragangliomas in asymptomatic carriers of SDHD and SDHB gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2012.203"}], "href": "https://doi.org/10.1038/ejhg.2012.203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22948026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22948026"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Attje S Hoekstra, Jean-Pierre Bayley "}, {"type": "b", "children": [{"type": "t", "text": "The role of complex II in disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2012.11.005"}], "href": "https://doi.org/10.1016/j.bbabio.2012.11.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23174333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23174333"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Bora E Baysal "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial complex II and genomic imprinting in inheritance of paraganglioma tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2012.12.005"}], "href": "https://doi.org/10.1016/j.bbabio.2012.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23291190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23291190"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Maria A Pantaleo, Annalisa Astolfi, Milena Urbini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of all subunits, SDHA, SDHB, SDHC, SDHD, of the succinate dehydrogenase complex in KIT/PDGFRA wild-type GIST."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2013.80"}], "href": "https://doi.org/10.1038/ejhg.2013.80"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23612575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23612575"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Jean-Pierre Bayley, Rogier A Oldenburg, Jennifer Nuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paraganglioma and pheochromocytoma upon maternal transmission of SDHD mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-014-0111-8"}], "href": "https://doi.org/10.1186/s12881-014-0111-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25300370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25300370"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Nicolasine D Niemeijer, Thomas G Papathomas, Esther Korpershoek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2015-2689"}], "href": "https://doi.org/10.1210/jc.2015-2689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26259135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26259135"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Sosipatros A Boikos, Alberto S Pappo, J Keith Killian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaoncol.2016.0256"}], "href": "https://doi.org/10.1001/jamaoncol.2016.0256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27011036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27011036"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Emily F Mason, Jason L Hornick "}, {"type": "b", "children": [{"type": "t", "text": "Conventional Risk Stratification Fails to Predict Progression of Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors: A Clinicopathologic Study of 76 Cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0000000000000685"}], "href": "https://doi.org/10.1097/PAS.0000000000000685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27340750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27340750"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Katrina A Andrews, David B Ascher, Douglas Eduardo Valente Pires, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SDHB"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SDHC"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SDHD"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2017-105127"}], "href": "https://doi.org/10.1136/jmedgenet-2017-105127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29386252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29386252"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "David Taïeb, George B Wanna, Maleeha Ahmad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Diabetes Endocrinol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S2213-8587(23)00038-4"}], "href": "https://doi.org/10.1016/S2213-8587(23"}, {"type": "t", "text": "00038-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37011647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37011647"}]}]}]}