Characterization of germline TP53 splicing mutations and their genetic andfunctional analysis

Germline TP53 splicing mutations have been described infrequently (>2%) in the literature, however in a series of 40 patients and families identified by our group in which there are germline TP53 mutations, seven affect splic ing (18%), The low figure reported in the literature might reflect the meth od of mutation detection, which in many studies does not include all splice junctions, These data indicate that a significant proportion of TP53 germl ine mutations are currently unrecognized. We have carried out detailed stud ies of the effects of the different mutations on splicing, and see distinct variations in the effects of the same mutation in different patients, Furt hermore we have identified the usage of a nonconsensus splice donor site in four families with an intron 4 splice donor mutation.