Hereditary paraganglioma (PGL)
2002-02-01 Anne-Paule Gimenez-Roqueplo AffiliationDépartement de Génétique Moléculaire, Hôpital Européen Georges Pompidou, 20-40, rue Leblanc, 75908 Paris cedex 15, France
Identity
Name
Hereditary paraganglioma (PGL)
Alias
Familial nonchromaffin paragangliomas , Familial glomus tumors , Chemodectomas , Carotid body tumors , Glomus jugulare tumors
Inheritance
Follows an autosomal dominant pattern. This pattern is associated with a maternal genomic imprinting for SDHD gene
, 35% of head and neck paragangliomas are inherited.
, 35% of head and neck paragangliomas are inherited.
Omim
115310 , 168000 , 601650 , 605373
Mesh
D010235
Orphanet
29072 Hereditary pheochromocytoma-paraganglioma
Umls
-
Clinics
Phenotype and clinics
Paragangliomas are highly vascularized tumors derived from neuroectodermal cells. In the familial forms, they are preferentially localized in the head and neck, in the carotid body (80%) and in the glomus jugulare (20%). They may be associated with other neural-crest-derived tumors such as pheochromocytomas. Individuals with familial paragangliomas have a more severe presentation (early age at onset and tumors at multiple sites) than do those with sporadic disease.
Neoplastic risk
Tumors are usually benign. Their gravity result of local invasion and important vascularisation. Among 10% of paraganglioma have a malignant evolution.
Treatment
Early detection and surgery
Prognosis
depends on extent of the disease at the time of diagnosis
Genes involved and Proteins
Alias
SDH4
Description
4 exons
Expression
wide
Function
SDHD encodes a mitochondrial respiratory-chain protein of complex II called \"cybS\"or small subunit of cytochrome b in succinate-ubiquinone oxidoreductase.
Germinal
Germ-line mutations in PGL patients are heterozygous and lead to protein truncation (false-sense mutations, insertions and deletions). Missense mutations are also described.
Somatic
Loss of wild type allele was usually observed in accordance with the two-hit model for neoplasia.
Alias
SDH3
Description
7 exons
Expression
wide
Function
SDHC encodes a mitochondrial respiratory-chain protein of complex II called \"cybL\"or large subunit of cytochrome b in succinate-ubiquinone oxidoreductase. This protein participates with cybS to the anchorage of the complex II in the innner mitochondrial membrane.
Germinal
Destruction of start codon ATG by a G-to-A transition in exon 1 of SDHC.
Somatic
Loss of wild type allele in tumor DNA.
Alias
SDH1
Description
8 exons
Expression
wide
Function
SDHB encodes a mitochondrial respiratory-chain protein of complex II called iron-sulfur protein. This protein participates with the flavoprotein, encoded by SDHA gene, to the enzymatic reaction which proceed to the oxydation of succinate in fumarate coupled with the reduction of ubiquinone to ubiquinol.
Germinal
Missense mutation leading to protein truncation.
Somatic
Not determined.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11404820 | 2001 | Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. | Astuti D et al |
| 10657297 | 2000 | Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. | Baysal BE et al |
| 11605159 | 2001 | The 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. | Gimenez-Roqueplo AP et al |
| 11343322 | 2001 | Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma. | Milunsky JM et al |
| 11062460 | 2000 | Mutations in SDHC cause autosomal dominant paraganglioma, type 3. | Niemann S et al |
| 11391798 | 2001 | Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene. | Taschner PE et al |
| 2574254 | 1989 | Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory. | van der Mey AG et al |
External Links
Citation
Anne-Paule Gimenez-Roqueplo
Hereditary paraganglioma (PGL)
Atlas Genet Cytogenet Oncol Haematol. 2002-02-01
Online version: http://atlasgeneticsoncology.org/cancer-prone-disease/10043/hereditary-paraganglioma-(pgl)
