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Familial Cancer

, Volume 6, Issue 3, pp 311–316

First Online: 23 February 2007Received: 08 December 2006Accepted: 18 December 2006DOI: 10.1007-s10689-006-9115-7

Cite this article as: van Hest, L.P., Ruijs, M.W.G., Wagner, A. et al. Familial Cancer 2007 6: 311. doi:10.1007-s10689-006-9115-7


Li-Fraumeni syndrome LFS is an autosomal dominantly inherited cancer predisposition syndrome characterized by a combination of tumors including sarcoma, breast cancer, brain tumors, adrenocortical carcinoma and leukemia. Germline mutations in the tumor suppressor gene TP53 are associated with LFS. We present a family with LFS in which initially a novel germline TP53 intron 5 splice site mutation was found. A second germline TP53 mutation, the exon 7 Asn235Ser 704A→ G mutation, was detected in this family through pre-symptomatic DNA testing. This latter mutation has been reported repeatedly in the literature as a pathogenic mutation involved in LFS. We provide evidence for pathogenicity of the novel intron 5 splice site mutation, whereas this evidence is lacking for the exon 7 Asn235Ser 704A→ G mutation. Our findings emphasize the importance of performing additional tests in case of germline sequence variants with uncertain functional effects.

KeywordsFunctional assay Li-Fraumeni syndrome TP53 germline mutations Unclassified variants Liselotte P. van Hest and Mariëlle W.G. Ruijs contributed equally to this work.

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Autor: Liselotte P. van Hest - Mariëlle W. G. Ruijs - Anja Wagner - Conny A. van der Meer - Senno Verhoef - Laura J. van‘


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