Connexion

GENATLAS PHENOTYPE

last update : 14-02-2009

Symbol	PGL1
Location	11q23.1
HGNC id	8900
Name	hereditary paraganglioma 1
Other name(s)	non chromaffin, chemodectoma carotid body tumors paraganglioma, familial nonchromaffin, 1
Corresponding gene	SDHD
Other symbol(s)	CBT1, PGL
Main clinical features	genetic predisposition to the development of slow-growing, highly vascular, generally benign neoplasms, usually of the head and neck with the carotid body as the major tumor site, and/or pheochromocytoma, hormonally active paraganglioma with adrenal medulla as the major site
Genetic determination	autosomal dominant
Prevalence	50p 100 of all paraganglioma
Related entries	TSG11F, PGL2, PGL3, PGL4
Function/system disorder	neoplasia
	endocrinology
Type	disease

Gene product

Name

D subunit of the succinate dehydrogenase mitochondrial complex II gene ; tumor suppressor gene

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

various types			germline mutations, with a commoness P81L mutation in exon 3 resulting of both a founder effect and recurrent mutations
deletion			gross SDHD deletions identified by multiplex PCR

Remark(s)

mutations in SDHD are the leading cause of head and neck paragangliomas

in familial cases, affected individuals inherit the disease gene from their father, suggesting genomic imprinting

PGL mutations could lead to constitutive activation of hypoxia signalling pathways

SDHD p.Cys11X mutation is a founding mutation associated with a high penetrance for paraganglial tumors of the skull base, neck, thorax, and retroperitoneum in the first four decades of life and, rarely, with malignancy (Pczkowska 2008)

Genotype/Phenotype correlations

SDHD mutation carriers, in addition to head and neck paragangliomas should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma