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GENATLAS PHENOTYPE

last update : 04-01-2012

Symbol	LFS1
Location	17p13.1
Name	Li-Fraumeni syndrome 1
Other name(s)	Sarcoma family syndrome of Li and Fraumeni SBLA syndrome
Corresponding gene	TP53
Other symbol(s)	BCCR
Main clinical features	familial cancer syndrome predisposing to osteosarcomas, soft-tissue sarcomas, premenopausal breast cancer, brain tumors, adrenal cortical tumors, and acute leukemias the spectrum of tumors is much broader than these original six component tumors cancer diagnosed before 33 years of age (Bougeard 2008)
Genetic determination	autosomal dominant
Prevalence	fewer than 400 families reported worldwide
Related entries	TSG17A
Function/system disorder	multisystem/generalized
	neoplasia
Type	disease

Gene product

Name

cellular tumor antigen p53 protein (TP53) implicated in cell cycle control after DNA damage and in apoptosis

Mechanism(s)

Gene mutation	Effect	Comments

missense	abnormal protein/gain of function	The majority of reported TP53 mutations are missense mutations, mostly in the core DNA-binding region of the gene.
abnormal splicing		Mutations affecting splice site junctions have been reported.

Remark(s)

mutation identified in about 50 percent of affected families, more than 250 distinct germline TP53 mutations have been described

Genotype/Phenotype correlations

while frame shift mutations have consistently been associated with high cancer risks, certain missense TP53 mutations may confer lower cancer risks.

missense mutations associated with a 9 year earlier tumour onset ( confirm that missense mutations not only inactivate TP53 but also have an additional oncogenic effect) (Bougeard 2008)