[Li-Fraumeni syndrome].
The Li-Fraumeni syndrome is an autosomal dominant syndrome representing a genetic predisposition to a wide spectrum of tumours including sarcomas, breast carcinomas, brain tumors and adrenocortical carcinomas. In most of the cases, tumours will develop in children and young adults. Germline mutations of the tumor suppressor gene p53 have been identified in approximately 50% of the families. In most of the cases, germline p53 mutations are missense mutations, located between exon 5 and exon 8, within the DNA-binding domain of p53. Since these mutations inactivate the transcriptional activity of the protein, they can easily be detected by analyzing in yeast the transcriptional competence of p53 cDNA derived from lymphocytes. The presence of a germline p53 mutations must be considered in: (1) families including two first degree relatives with cancers belonging to the Li-Fraumeni spectrum, one relative being affected before age 45; (2) children or young adults with a rare tumour of in the general population, belonging to the Li-Fraumeni spectrum, such as adrenocortical carcinoma; and (3) children or young adults under age 45 with multiple primary tumours of the Li-Fraumeni spectrum. Identification of a germline p53 mutation in an affected subject allows to establish the diagnosis of the Li-Fraumeni syndrome on a molecular basis.
Frebourg
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Laboratoire de génétique moléculaire, Hôpital Charles-Nicolle, Centre hospitalo-universitaire de Rouen, France.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D008040:Genetic Linkage; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007223:Infant; D016864:Li-Fraumeni Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D010375:Pedigree