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Open Access 01-12-2006 | Research article

Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

Authors: Jean-Pierre Bayley, Ivonne van Minderhout, Marjan M Weiss, Jeroen C Jansen, Peter HN Oomen, Fred H Menko, Barbara Pasini, Barbara Ferrando, Nora Wong, Lesley C Alpert, Rosie Williams, Edward Blair, Peter Devilee, Peter EM Taschner

Published in: BMC Medical Genetics | Issue 1/2006

Abstract

Background

Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle and the mitochondrial respiratory chain (succinate:ubiquinone oxidoreductase or complex II).

Methods

Using conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing to analyse genomic DNA from peripheral blood lymphocytes, here we describe the mutation analysis of the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family history) head and neck paraganglioma and five pheochromocytoma and/or paraganglioma families.

Results

Two sporadic patients were found to have a SDHB splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys) missense mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif that constitutes the quinone-binding site of the succinate: ubiquinone oxidoreductase (SQR) complex in E. coli. Together with our previous results, we found 27 germline mutations of SDH genes in 95 cases (28%) of sporadic head and neck paraganglioma. In addition all index patients of five families showing hereditary pheochromocytoma-paraganglioma were found to carry germline mutations of SDHB: four of which were novel, c.343C>T (p.Arg115X), c.141G>A (p.Trp47X), c.281G>A (p.Arg94Lys), and c.653G>C (p.Trp218Ser), and one reported previously, c.136C>T, p.Arg46X.

Conclusion

In conclusion, these data indicate that germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma and further underline the importance of germline SDHB mutations in cases of familial pheochromocytoma-paraganglioma.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/7/1/prepub

Title: Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma
Authors: Jean-Pierre Bayley
Ivonne van Minderhout
Marjan M Weiss
Jeroen C Jansen
Peter HN Oomen
Fred H Menko
Barbara Pasini
Barbara Ferrando
Nora Wong
Lesley C Alpert
Rosie Williams
Edward Blair
Peter Devilee
Peter EM Taschner
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2006
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-7-1

At a glance: The STEP trials

Springer Medicine

Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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