Loading...
Please wait, while we are loading the content...
Similar Documents
Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma
| Content Provider | Open Access Library (OALib) |
|---|---|
| Author | 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 |
| Abstract | 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.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.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.Paragangliomas (PGL) of the head and neck (also known as glomus tumors) are parasympathetically innervated, benign tumors, most commonly arising at the carotid bifurcation, but also frequently found as vagal and jugulotympanic tumors. Pheochromocytomas are paragangliomas of the sympathetic nervous system, frequently catecholamine-secreting and arising in the chromaffin cells of the adrenal medulla. Extra-adrenal paragangliomas (often described as extra-adrenal pheo |
| ISSN | 14712350 |
| Journal | BMC Medical Genetics |
| DOI | 10.1186/1471-2350-7-1 |
| Publisher | BioMed Central |
| Publisher Date | 2006-01-01 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
