| Written | 2002-02 | Anne-Paule Gimenez-Roqueplo |
| Département de Génétique Moléculaire, Hôpital Européen Georges Pompidou, 20-40, rue Leblanc, 75908 Paris cedex 15, France |
| Identity |
| Other names | Familial nonchromaffin paragangliomas |
| Familial glomus tumors | |
| Chemodectomas | |
| Carotid body tumors | |
| Glomus jugulare tumors | |
| Atlas_Id | 10043 |
| Genes implicated in | SDHAF2 SDHB SDHC SDHD MAX MEN2 NF1 SDHA TMEM127 VHL |
| 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. |
| 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 |
| Gene Name | SDHD |
| Alias | SDH4 |
| Location | 11q23 |
| DNA/RNA | |
| Description | 4 exons |
| Protein | |
| Description | The corresponding protein has 159 amino acids (17 kDa). The 1 to 56 amino acids encode the transit peptide and the 57 to 159 amino acids the mature protein. |
| 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. |
| Mutations | |
| 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. |
| Gene Name | SDHC |
| Alias | SDH3 |
| Location | 1q21 |
| DNA/RNA | |
| Description | 7 exons |
| Protein | |
| Description | 140 amino acids (15 kDa) |
| 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. |
| Mutations | |
| 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. |
| Gene Name | SDHB |
| Alias | SDH1 |
| Location | 1p36.1-p35 |
| DNA/RNA | |
| Description | 8 exons |
| Protein | |
| Description | 252 amino acids (27 kDa) |
| 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. |
| Mutations | |
| Germinal | Missense mutation leading to protein truncation. |
| Somatic | Not determined. |
| Bibliography |
| Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. |
| Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, Sköldberg F, Husebye ES, Eng C, Maher ER |
| American journal of human genetics. 2001 ; 69 (1) : 49-54. |
| PMID 11404820 |
| Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. |
| Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B |
| Science (New York, N.Y.). 2000 ; 287 (5454) : 848-851. |
| PMID 10657297 |
| 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, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rötig A, Jeunemaitre X |
| American journal of human genetics. 2001 ; 69 (6) : 1186-1197. |
| PMID 11605159 |
| Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma. |
| Milunsky JM, Maher TA, Michels VV, Milunsky A |
| American journal of medical genetics. 2001 ; 100 (4) : 311-314. |
| PMID 11343322 |
| Mutations in SDHC cause autosomal dominant paraganglioma, type 3. |
| Niemann S, Müller U |
| Nature genetics. 2000 ; 26 (3) : 268-270. |
| PMID 11062460 |
| Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene. |
| Taschner PE, Jansen JC, Baysal BE, Bosch A, Rosenberg EH, Bröcker-Vriends AH, van Der Mey AG, van Ommen GJ, Cornelisse CJ, Devilee P |
| Genes, chromosomes & cancer. 2001 ; 31 (3) : 274-281. |
| PMID 11391798 |
| Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory. |
| van der Mey AG, Maaswinkel-Mooy PD, Cornelisse CJ, Schmidt PH, van de Kamp JJ |
| Lancet. 1989 ; 2 (8675) : 1291-1294. |
| PMID 2574254 |
| Citation |
| This paper should be referenced as such : |
| Gimenez-Roqueplo, AP |
| Hereditary paraganglioma (PGL) |
| Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):143-144. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Tumors/HeredParagangID10043.html |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:24:24 CEST 2017 |
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