Endocrine

, Volume 38, Issue 1, pp 18–23 | Cite as

L157X nonsense mutation of the succinate dehydrogenase subunit B gene in a Japanese patient with right paraaortic paraganglioma

  • Haruhiro Sato
  • Genta Kanai
  • Kenichi Hirabayshi
  • Hiroshi Kajiwara
  • Johbu Itoh
  • Robert Yoshiyuki Osamura
Case Report

Abstract

Nuclear genes succinate dehydrogenase B subunit and succinate dehydrogenase D subunit, which encode two mitochondrial complex II subunits, are associated with the development of familial paraganglioma (PGL). Succinate dehydrogenase B subunit gene mutation is highly associated with extraadrenal PGL and subsequent distant metastasis. We describe the case of a 29-year-old Japanese man with a 3-year history of hypertension, headache, and palpitation. Endocrinological examinations showed that the patient had elevated levels of catecholamines, and imaging studies revealed a right paraaortic PGL without distant metastases. The PGL was surgically removed. Genetic analysis of the patient showed a heterozygous thymine deletion at position 470 (c.470delT) in exon 5 of the succinate dehydrogenase B subunit gene complementary DNA. This thymine deletion changed TTG (leucine) to TGA (stop codon) at codon 157 (L157X). It remains unclear whether this mutation was associated with PGL malignancy because the patient has had no metastases for the past 3 years. It has been recently reported that L157X is associated with malignant paraaortic PGL. Thus, strict follow-up is required because this succinate dehydrogenase B subunit gene’s nonsense mutation (L157X) may be related to the malignancy.

Keywords

Paraganglioma SDHB L157X Malignancy 

Notes

Acknowledgments

The authors thank Mr. Hiroshi Kamiguchi and Ms. Michiyo Yoshino from the Teaching and Research Support Center of the Tokai University School of Medicine for their technical assistance.

References

  1. 1.
    R.A. DeLellis, R.V. Lloyd, P.U. Heitz, C. Eng (eds.), Pathology and Genetics: WHO Classification of Tumours of Endocrine Organs (IARC Press, Lyon, 2004), pp. 147–166Google Scholar
  2. 2.
    H.J.L. Timmers, A. Kozupa, G. Eisenhofer, M. Raygada, K.T. Adams, D. Solis, J.W.M. Lenders, K. Pacak, Clinical presentations, biochemical phenotypes, and genotype-phenotype correlation in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J. Clin. Endocrinol. Metab. 92, 779–786 (2007)CrossRefPubMedGoogle Scholar
  3. 3.
    F. Sun, X. Huo, Y. Zhai, A. Wang, J. Xu, D. Su, M. Bartlam, Z. Rao, Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 121, 1043–1057 (2005)CrossRefPubMedGoogle Scholar
  4. 4.
    D. Astuti, F. Latif, A. Dallol, P.L. Dahia, F. Douglas, E. George, F. Sköldberg, E.S. Husebye, C. Eng, E.R. Maher, Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am. J. Hum. Genet. 69, 49–54 (2001)CrossRefPubMedGoogle Scholar
  5. 5.
    D.E. Benn, A.P. Gimenez-Roqueplo, J.R. Reilly, J. Bertheral, J. Burgess, K. Byth, M. Croxson, P.L. Dahia, M. Elston, O. Gimm, D. Henley, P. Herman, V. Murday, P. Niccoli-Sire, J.L. Pasieka, V. Rohmer, K. Tucker, X. Jeunemaitre, D.J. Marsh, P.F. Plouin, B.G. Robinson, Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J. Clin. Endocrinol. Metab. 91, 827–836 (2006)CrossRefPubMedGoogle Scholar
  6. 6.
    A.P. Gimenez-Roqueplo, J. Favier, P. Rustin, C. Rieubland, M. Crespin, V. Nau, P. Khau Van Kien, P. Corvol, P.F. Plouin, X. Jeunemaitre, COMETE Network, Mutations in the SDHB gene are associated with extra-adrenal and/or malignant pheochromocytomas. Cancer Res. 63, 5615–5621 (2003)Google Scholar
  7. 7.
    H.P. Neumann, C. Pawlu, M. Peçzkowska, B. Bausch, S.R. McWhinney, M. Muresan, M. Buchta, G. Franke, J. Klisch, T.A. Bley, S. Hoegerle, C.C. Boedeker, G. Opocher, J. Schipper, A. Januszewicz, C. Eng, European-American Paraganglioma Study Group, Distinct clinical features of paraganglioma syndrome associated with SDHB and SDHD gene mutations. JAMA. 292, 943–951 (2004)Google Scholar
  8. 8.
    S. Niemann, U. Müller, Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat. Genet. 26, 268–270 (2000)CrossRefPubMedGoogle Scholar
  9. 9.
    M. Mannelli, T. Ercolino, V. Giachè, L. Simi, C. Cirami, G. Parenti, Genetic screening for pheochromocytoma: should SDHC gene analysis be included? J. Med. Genet. 44, 586–587 (2007)CrossRefPubMedGoogle Scholar
  10. 10.
    Z. Erlic, L. Rybicki, M. Peczkowska, H. Golcher, P.H. Kann, M. Brauckhoff, K. Müssig, M. Muresan, A. Schäffler, N. Reisch, M. Schott, M. Fassnacht, G. Opocher, S. Klose, C. Fottner, F. Forrer, U. Plöckinger, S. Petersenn, D. Zabolotny, O. Kollukch, S. Yaremchuk, A. Januszewicz, M.K. Walz, C. Eng, H.P. Neumann, European-American Pheochromocytoma Study Group, Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients. Clin. Cancer Res. 15, 6378–6385 (2009)Google Scholar
  11. 11.
    T. Bourgeron, P. Rustin, D. Chretien, M. Birch-Machin, M. Bourgeois, E. Viegas-Péquignot, A. Munnich, A. Rötig, Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat. Genet. 11, 144–149 (1995)CrossRefPubMedGoogle Scholar
  12. 12.
    B.E. Baysal, R.E. Ferrell, J.E. Willett-Brozick, E.C. Lawrence, D. Myssiorek, A. Bosch, A. van der Mey, P.E. Taschner, W.S. Rubinstein, E.N. Myers, C.W. Richard 3rd, C.J. Cornelisse, P. Devilee, B. Devlin, Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287, 848–851 (2000)CrossRefPubMedGoogle Scholar
  13. 13.
    T. Saito, Y. Saito, K. Matsumura, Y. Tsubota, T. Maniwa, H. Kaneda, K. Minami, N. Sakaida, Y. Uemura, G. Kawa, N. Yamamoto, Y. Fujii, K. Isobe, Y. Kawakami, T. Matsuda, K. Takekoshi, Novel mutation (L157X) in the succinate dehydrogenase Bgene (SDHB) in a Japanese family with abdominal paraganglioma following lung metastasis. Endocr. J. 56, 451–458 (2009)CrossRefPubMedGoogle Scholar
  14. 14.
    S. Majumdar, C.A. Friedrich, C.A. Koch, G.C. Megason, J.D. Fratkin, G.W. Moll, Compound heterozygous mutation with a novel splice donor region DNA sequence variant in the succinate dehydrogenase subunit B gene in malignant paraganglioma. Pediatr. Blood Cancer 54, 473–475 (2010)CrossRefPubMedGoogle Scholar
  15. 15.
    M. Naito, T. Usui, T. Tamanaha, S.T. Kawashima, H. Iogawa, H. Hagiwara, T. Kimura, T. Tagami, M. Kurosawa, A. Shimatsu, M. Naruse, R27X nonsense mutation of the SDHB gene in a patient with sporadic malignant paraganglioma. Endocrine 36, 10–15 (2009)CrossRefPubMedGoogle Scholar
  16. 16.
    L. Amar, J. Bertherat, E. Baudin, C. Ajzenberg, B. Bressac-de Paillerets, O. Chabre, B. Chamontin, B. Delemer, S. Giraud, A. Murat, P. Niccoli-Sire, S. Richard, V. Rohmer, J.L. Sadoul, L. Strompf, M. Schlumberger, X. Bertagna, P.F. Plouin, X. Jeunemaitre, A.P. Gimenez-Roqueplo, Genetic testing in pheochromocytoma or functional paraganglioma. J. Clin. Oncol. 23, 8812–8818 (2005)Google Scholar
  17. 17.
    H.J.L. Timmer, A.P. Gimenez-Roqueplo, M. Mannelli, K. Pacak, Clinical aspects of SDHx-related pheochromocytoma and paraganglioma. Endocr. Relat. Cancer 16, 391–400 (2009)CrossRefGoogle Scholar
  18. 18.
    C.J. Ricketts, J.R. Forman, E. Rattenberry, N. Bradshaw, F. Lalloo, L. Izatt, T.R. Cole, R. Armstrong, V.K. Kumar, P.J. Morrison, A.B. Atkinson, F. Douglas, S.G. Ball, J. Cook, U. Srirangalingam, P. Killick, G. Kirby, S. Aylwin, E.R. Woodward, D.G. Evans, S.V. Hodgson, V. Murday, S.L. Chew, J.M. Connell, T.L. Blundell, F. MacDonald, E.R. Maher, Tumor risks and genotype–phenotype–proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum. Mutat. 31, 41–51 (2009)CrossRefGoogle Scholar
  19. 19.
    A.P. Gimenez-Roqueplo, J. Favier, P. Rustin, C. Rieubland, V. Kerlan, P.F. Plouin, A. Rötig, X. Jeunemaitre, Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J. Clin. Endocrinol. Metab. 87, 4771–4774 (2002)CrossRefPubMedGoogle Scholar
  20. 20.
    H.P. Neumann, B. Bausch, S.R. McWhinney, B.U. Bender, O. Gimm, G. Franke, J. Schipper, J. Klisch, C. Altehoefer, K. Zerres, A. Januszewicz, C. Eng, The Freiburg-Warsaw-Columbus Pheochromocytoma Study Group, Germ-line mutations in nonsyndromic pheochromocytoma. N. Engl. J. Med. 346, 1459–1466 (2002)CrossRefPubMedGoogle Scholar
  21. 21.
    D.E. Benn, M.S. Croxson, K. Tucker, C.P. Bambach, A.L. Richardson, L. Delbridge, P.T. Pullan, J. Hammond, D.J. Marsh, B.G. Robinson, Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytoma. Oncogene. 22, 1358–1364 (2003)Google Scholar
  22. 22.
    S. Vanharanta, M. Buchta, S.R. McWhinney, S.K. Virta, M. Peczkowska, C.D. Morrison, R. Lehtonen, A. Januszewicz, H. Jarvinen, M. Juhola, J.P. Mecklin, E. Pukkala, R. Herva, M. Kiuru, N.N. Nupponen, L.A. Aaltonen, H.P. Neumann, C. Eng, Early-onset renal cell carcinoma as a novel extraparaganglioma component of SDHB-associated heritable paraganglioma. Am. J. Hum. Genet. 74, 53–159 (2004)CrossRefGoogle Scholar
  23. 23.
    Y. Ni, K.M. Zbuk, T. Sadler, A. Patocs, G. Lobo, E. Edelman, P. Platzer, M.S. Orloff, K.A. Waite, C. Eng, Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. Am. J. Hum. Genet. 83, 261–268 (2008)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Haruhiro Sato
    • 1
  • Genta Kanai
    • 1
  • Kenichi Hirabayshi
    • 2
  • Hiroshi Kajiwara
    • 2
  • Johbu Itoh
    • 2
  • Robert Yoshiyuki Osamura
    • 2
  1. 1.Department of MedicineTokai University School of MedicineIseharaJapan
  2. 2.Department of PathologyTokai University School of MedicineIseharaJapan

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