Abstract
Familial catecholamine secreting tumors have been associated with multiple endocrine neoplasia type 2, Von Hippel-Lindau disease and neurofibromatosis type 1. In the last years, mutations of genes encoding subunits B, C and D of the succinate dehydrogenase have been discovered as other causes of pheochromocytomas and paragangliomas. We diagnosed a malignant retroperitoneal paraganglioma in a 64-yr-old man with bone metastasis in 2001. Two years later a retroperitoneal benign paraganglioma was found and resected in his 32-yr-old daughter. Thus we diagnosed in this family a paraganglioma syndrome. We performed molecular genetic analyses of the genes SDHB, SDHC, and SDHD. We detected in the SDHB gene the mutation SDHB c. 558–3 C>G affecting the splice site of exon 5. In a second daughter the mutation was also detected, thorough clinical investigation revealed normal results. We conclude that the SDHB mutation predisposes to abdominal extra-adrenal and potential malignant pheochromocytoma with incomplete penetrance.
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Baysal BE, Ferrel RE, Willett-Brozick JE, et al. Mutations in the SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000, 287: 848–51.
Astuti D, Douglas F, Lennard TW, et al. Germline SDHD mutation in familial pheochromocytoma. Lancet 2001, 357: 1181–2.
Astuti D, Latif F, Dallol A, et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial phechromocytoma and to familial paraganglioma. Am J Hum Genet 2001, 69: 49–54.
Neumann HPH, Bausch B, McWhinney SR, et al. Germline mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002, 346: 1459–66.
DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003, 348: 2656–68.
Gimenez-Roqueplo AP, Favier J, Rustin P, et al. 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. Am J Hum Genet 2001, 69: 1186–97.
Neumann HPH, Pawlu C, Peczkowska M, et al. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 2004, 292: 943–51.
Gimenez-Roqueplo AP, Favier J, Rustin P, et al. Functional consequences of a SDHB gene mutation in an apparently sporadic phechromocytoma. J Clin Endocrinol Metab 2002, 87: 4771–4.
Young AL, Baysal BE, Deb A, Young WF Jr. Familial malignant catecholamine secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. J Clin Endocriol Metab 2002, 87: 4101–5.
Aguiar RC, Cox G, Pomeroy SL, Dahia PL. Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL 1), in pheochromocytomas. J Clin Endocrinol Metab 2001, 86: 2890–4.
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Fuentes Gómez, C., Menéndez, E., Pineda, J. et al. The malignant potential of a succinate dehydrogenase subunit B germline mutation. J Endocrinol Invest 29, 350–352 (2006). https://doi.org/10.1007/BF03344107
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DOI: https://doi.org/10.1007/BF03344107