Hereditary paraganglioma (PGL)

2002-02-01   Anne-Paule Gimenez-Roqueplo 

Département 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.

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.

Bibliography

Pubmed IDLast YearTitleAuthors
114048202001Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.Astuti D et al
106572972000Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.Baysal BE et al
116051592001The 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
113433222001Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.Milunsky JM et al
110624602000Mutations in SDHC cause autosomal dominant paraganglioma, type 3.Niemann S et al
113917982001Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene.Taschner PE et al
25742541989Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory.van der Mey AG et al

External Links