Skip to main content

Advertisement

SpringerLink
Log in

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

  • Case Report
  • Published:
Endocrine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  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. 147–166

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

  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. S. Niemann, U. Müller, Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat. Genet. 26, 268–270 (2000)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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. 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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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. 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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

  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. 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)

    Article  Google Scholar 

  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)

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa, 259-1193, Japan

    Haruhiro Sato & Genta Kanai

  2. Department of Pathology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa, 259-1193, Japan

    Kenichi Hirabayshi, Hiroshi Kajiwara, Johbu Itoh & Robert Yoshiyuki Osamura

Authors
  1. Haruhiro Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Genta Kanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenichi Hirabayshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroshi Kajiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Johbu Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Yoshiyuki Osamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haruhiro Sato.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sato, H., Kanai, G., Hirabayshi, K. et al. L157X nonsense mutation of the succinate dehydrogenase subunit B gene in a Japanese patient with right paraaortic paraganglioma. Endocr 38, 18–23 (2010). https://doi.org/10.1007/s12020-010-9365-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-010-9365-x

Keywords

Search

Navigation