Skip to main content

Advertisement

SpringerLink
Log in

Mutations of the SDHB and SDHD genes

  • Review
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

The succinate dehydrogenase (SDH) is a mitochondrial enzyme complex with an important role in oxydative phosphorylation and intracellular oxygene sensing and signaling. Mutations in the SDHB (1p35–36) and SDHD subunits (11q23) give rise to the paraganglioma syndromes (PGL), namely PGL 4 and PGL 1, and generate paraganglioma and pheochromocytoma. For both genes mutations have been described that result in a loss of function of the gene products. SDHBmutations were found in five of eight exons and in two introns, SDHD mutations in all four exons and one intron. Phenotypes and rate of malignancy of SDHB and SDHD seem to be different, with a higher frequency of head-and-neck tumors in SDHD and indications of a higher risk of malignancy in SDHB mutations. As routine diagnostic procedure all SDH mutation carriers should have urine catecholamine analysis as well as pelvic, abdominal, thoracic and skull/neck MRI.

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

Similar content being viewed by others

References

  1. HP Neumann B Bausch SR. McWhinney et al. (2002) ArticleTitleGerm-line mutations in nonsyndromic pheochromocytoma N Engl J Med 346 1459 Occurrence Handle10.1056/NEJMoa020152 Occurrence Handle1:CAS:528:DC%2BD38XjsVynsLc%3D Occurrence Handle12000816

    Article  CAS  PubMed  Google Scholar 

  2. BE Baysal WS. Rubinstein (2001) ArticleTitleTaschner PE Phenotypic dichotomy in mitochondrial complex II genetic disorders. J Mol Med 79 495 Occurrence Handle1:CAS:528:DC%2BD3MXot1GhtL8%3D

    CAS  Google Scholar 

  3. T Bourgeron P Rustin D. Chretien et al. (1995) ArticleTitleMutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency Nat Genet 11 144 Occurrence Handle10.1038/ng1095-144 Occurrence Handle1:CAS:528:DyaK2MXosF2rtr8%3D Occurrence Handle7550341

    Article  CAS  PubMed  Google Scholar 

  4. AP Gimenez-Roqueplo J Favier P. Rustin et al. (2001) ArticleTitleThe 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 69 1186 Occurrence Handle10.1086/324413 Occurrence Handle1:CAS:528:DC%2BD38XhslShsw%3D%3D Occurrence Handle11605159

    Article  CAS  PubMed  Google Scholar 

  5. AP Gimenez-Roqueplo J Favier P. Rustin et al. (2002) ArticleTitleFunctional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma J Clin Endocrinol Metab 87 4771 Occurrence Handle10.1210/jc.2002-020525 Occurrence Handle1:CAS:528:DC%2BD38XnvFCrtr0%3D Occurrence Handle12364472

    Article  CAS  PubMed  Google Scholar 

  6. PH. Maxwell MS Wiesener GW. Chang et al. (1999) ArticleTitleThe tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis Nature 399 271 Occurrence Handle10.1038/20459 Occurrence Handle1:CAS:528:DyaK1MXjsFyqt74%3D Occurrence Handle10353251

    Article  CAS  PubMed  Google Scholar 

  7. P Heutink AG Mey Particlevan der LA. Sandkuijl et al. (1992) ArticleTitleA gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter Hum Mol Genet 1 7 Occurrence Handle1:CAS:528:DyaK38Xkt1WgtLg%3D Occurrence Handle1301144

    CAS  PubMed  Google Scholar 

  8. BE. Baysal (2002) ArticleTitleHereditary paraganglioma targets diverse paraganglia J Med Genet 39 617 Occurrence Handle10.1136/jmg.39.9.617 Occurrence Handle1:CAS:528:DC%2BD38XnvVeqs7w%3D Occurrence Handle12205103

    Article  CAS  PubMed  Google Scholar 

  9. AP Gimenez-Roqueplo J Favier P. Rustin et al. (2003) ArticleTitleMutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas Cancer Res 63 5615 Occurrence Handle1:CAS:528:DC%2BD3sXntlers7g%3D Occurrence Handle14500403

    CAS  PubMed  Google Scholar 

  10. JW Lenders K Pacak MM. Walther et al. (2002) ArticleTitleBiochemical diagnosis of pheochromocytoma: which test is best? JAMA 287 1427 Occurrence Handle10.1001/jama.287.11.1427 Occurrence Handle1:CAS:528:DC%2BD38Xit1ersrw%3D Occurrence Handle11903030

    Article  CAS  PubMed  Google Scholar 

  11. HP Neumann DP Berger G. Sigmund et al. (1993) ArticleTitlePheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel–Lindau disease N Engl J Med 329 1531 Occurrence Handle10.1056/NEJM199311183292103 Occurrence Handle1:STN:280:ByuD3MbmsVY%3D Occurrence Handle8105382

    Article  CAS  PubMed  Google Scholar 

  12. S Hoegerle E Nitzsche C. Altehoefer et al. (2002) ArticleTitlePheochromocytomas: detection with 18F DOPA whole body PET–initial results Radiology 222 507 Occurrence Handle11818620

    PubMed  Google Scholar 

  13. S Hoegerle N Ghanem C. Altehoefer et al. (2003) ArticleTitle18F-DOPA positron emission tomography for the detection of glomus tumours Eur J Nucl Med Mol Imag 30 689 Occurrence Handle1:CAS:528:DC%2BD3sXjsF2ksb0%3D

    CAS  Google Scholar 

  14. K Pacak G Eisenhofer JA. Carrasquillo et al. (2001) ArticleTitle6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma Hypertension 38 6 Occurrence Handle1:CAS:528:DC%2BD3MXls1KhtLc%3D Occurrence Handle11463751

    CAS  PubMed  Google Scholar 

  15. I Ilias J Yu JA. Carrasquillo et al. (2003) ArticleTitleSuperiority of 6-[18F]-fluorodopamine positron emission tomography versus [131I]-metaiodobenzylguanidine scintigraphy in the localization of metastatic pheochromocytoma J Clin Endocrinol Metab 88 4083 Occurrence Handle10.1210/jc.2003-030235 Occurrence Handle1:CAS:528:DC%2BD3sXntlahtbc%3D Occurrence Handle12970267

    Article  CAS  PubMed  Google Scholar 

  16. E Benn D S Croxson M K. Tucker et al. (2003) ArticleTitleNovel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas Oncogene 22 1358 Occurrence Handle10.1038/sj.onc.1206300 Occurrence Handle12618761

    Article  PubMed  Google Scholar 

  17. BE Baysal JE Willett-Brozick EC. Lawrence et al. (2002) ArticleTitle). Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas J Med Genet 39 178 Occurrence Handle10.1136/jmg.39.3.178 Occurrence Handle1:CAS:528:DC%2BD38XivV2ktrY%3D Occurrence Handle11897817

    Article  CAS  PubMed  Google Scholar 

  18. D Astuti F Latif A. Dallol et al. (2001) ArticleTitleGene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma Am J Hum Genet 69 49 Occurrence Handle10.1086/321282 Occurrence Handle1:CAS:528:DC%2BD3MXls1emtrY%3D Occurrence Handle11404820

    Article  CAS  PubMed  Google Scholar 

  19. RF Badenhop S Cherian RS. Lord et al. (2001) ArticleTitleNovel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss Genes Chromosomes Cancer 31 255 Occurrence Handle10.1002/gcc.1142 Occurrence Handle1:CAS:528:DC%2BD3MXkslClsb4%3D Occurrence Handle11391796

    Article  CAS  PubMed  Google Scholar 

  20. O Gimm M Armanios H. Dziema et al. (2000) ArticleTitleSomatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma Cancer Res 60 6822 Occurrence Handle1:CAS:528:DC%2BD3MXjsVKrsQ%3D%3D Occurrence Handle11156372

    CAS  PubMed  Google Scholar 

  21. PE Taschner JC Jansen BE. Baysal et al. (2001) ArticleTitleNearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene Genes Chromosomes Cancer 31 274 Occurrence Handle10.1002/gcc.1144 Occurrence Handle1:CAS:528:DC%2BD3MXkslClsbw%3D Occurrence Handle11391798

    Article  CAS  PubMed  Google Scholar 

  22. D Astuti F Douglas TW. Lennard et al. (2001) ArticleTitleGermline SDHD mutation in familial phaeochromocytoma Lancet 357 1181 Occurrence Handle10.1016/S0140-6736(00)04378-6 Occurrence Handle1:CAS:528:DC%2BD3MXivFaqsbo%3D Occurrence Handle11323050

    Article  CAS  PubMed  Google Scholar 

  23. JM Milunsky TA Maher VV. Michels et al. (2001) ArticleTitleNovel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma Am J Med Genet 100 311 Occurrence Handle10.1002/ajmg.1270 Occurrence Handle1:STN:280:DC%2BD3MvntlOgtg%3D%3D Occurrence Handle11343322

    Article  CAS  PubMed  Google Scholar 

  24. BE Baysal RE Ferrell JE. Willett-Brozick et al. (2000) ArticleTitleMutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma Science 287 848 Occurrence Handle10.1126/science.287.5454.848 Occurrence Handle1:CAS:528:DC%2BD3cXhtVehtrs%3D Occurrence Handle10657297

    Article  CAS  PubMed  Google Scholar 

  25. A Cascon S Ruiz-Llorente A. Cebrian et al. (2002) ArticleTitleIdentification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma Eur J Hum Genet 10 457 Occurrence Handle10.1038/sj.ejhg.5200829 Occurrence Handle1:CAS:528:DC%2BD38XltFertLc%3D Occurrence Handle12111639

    Article  CAS  PubMed  Google Scholar 

  26. H Dannenberg WN Dinjens M. Abbou et al. (2002) ArticleTitleFrequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma Clin Cancer Res 8 2061 Occurrence Handle1:CAS:528:DC%2BD38XmtVWitLw%3D Occurrence Handle12114404

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology and Hypertension, Albert-Ludwigs-Universität, Freiburg, Germany

    Christian Pawlu, Birke Bausch & Hartmut P. H. Neumann

Authors
  1. Christian Pawlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Birke Bausch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hartmut P. H. Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hartmut P. H. Neumann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pawlu, C., Bausch, B. & Neumann, H.P.H. Mutations of the SDHB and SDHD genes. Familial Cancer 4, 49–54 (2005). https://doi.org/10.1007/s10689-004-4227-4

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-004-4227-4

Keywords

Search

Navigation