The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients
<p>Abstract</p> <p>Background</p> <p>Germline mutations of the tumor suppressor genes <it>SDHB, SDHC </it>and <it>SDHD </it>play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydro...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-04-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/10/34 |
| _version_ | 1818878209336279040 |
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| author | Devilee Peter Dullaart Robin PF Jansen Jeroen C Lenders Jacques W Kunst Henricus P van der Wielen Michiel van Bunderen Patrick A Grimbergen Anneliese EM Bayley Jean-Pierre Corssmit Eleonora P Vriends Annette H Losekoot Monique Weiss Marjan M |
| author_facet | Devilee Peter Dullaart Robin PF Jansen Jeroen C Lenders Jacques W Kunst Henricus P van der Wielen Michiel van Bunderen Patrick A Grimbergen Anneliese EM Bayley Jean-Pierre Corssmit Eleonora P Vriends Annette H Losekoot Monique Weiss Marjan M |
| author_sort | Devilee Peter |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Germline mutations of the tumor suppressor genes <it>SDHB, SDHC </it>and <it>SDHD </it>play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described.</p> <p>Methods</p> <p>We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation.</p> <p>Results</p> <p>A novel deletion of exon 3 of the <it>SDHB </it>gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the <it>SDHB </it>locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases.</p> <p>Conclusion</p> <p>The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch <it>SDHB </it>founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.</p> |
| first_indexed | 2024-12-19T14:10:32Z |
| format | Article |
| id | doaj.art-14184d58d89e4859a739fe430b2415ce |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-19T14:10:32Z |
| publishDate | 2009-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-14184d58d89e4859a739fe430b2415ce2022-12-21T20:18:08ZengBMCBMC Medical Genetics1471-23502009-04-011013410.1186/1471-2350-10-34The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patientsDevilee PeterDullaart Robin PFJansen Jeroen CLenders Jacques WKunst Henricus Pvan der Wielen Michielvan Bunderen Patrick AGrimbergen Anneliese EMBayley Jean-PierreCorssmit Eleonora PVriends Annette HLosekoot MoniqueWeiss Marjan M<p>Abstract</p> <p>Background</p> <p>Germline mutations of the tumor suppressor genes <it>SDHB, SDHC </it>and <it>SDHD </it>play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described.</p> <p>Methods</p> <p>We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation.</p> <p>Results</p> <p>A novel deletion of exon 3 of the <it>SDHB </it>gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the <it>SDHB </it>locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases.</p> <p>Conclusion</p> <p>The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch <it>SDHB </it>founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.</p>http://www.biomedcentral.com/1471-2350/10/34 |
| spellingShingle | Devilee Peter Dullaart Robin PF Jansen Jeroen C Lenders Jacques W Kunst Henricus P van der Wielen Michiel van Bunderen Patrick A Grimbergen Anneliese EM Bayley Jean-Pierre Corssmit Eleonora P Vriends Annette H Losekoot Monique Weiss Marjan M The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients BMC Medical Genetics |
| title | The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients |
| title_full | The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients |
| title_fullStr | The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients |
| title_full_unstemmed | The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients |
| title_short | The first Dutch <it>SDHB </it>founder deletion in paraganglioma – pheochromocytoma patients |
| title_sort | first dutch it sdhb it founder deletion in paraganglioma pheochromocytoma patients |
| url | http://www.biomedcentral.com/1471-2350/10/34 |
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