Most of the hereditary breast cancers are attributed to constitutive alterations of either BRCA1 or BRCA2 genes; nonetheless, germline mutations of these genes iǹ high risk' families are found less frequently than expected from linkage data. Recent ®ndings suggest that major genomic rearrangements of the BRCA1 gene might account for at least some of the apparently mutation negative cases. We studied 60 aected probands belonging to families with a strong history of breast and/or ovarian cancer who scored negative for BRCA1 gene mutations by PTT and SSCP analysis. DNA was analysed by the Southern blotting procedure using three dierent restriction enzymes, and two probes obtained by RT ± PCR of the 5' and 3' BRCA1 coding sequence. A 3 kb deletion encompassing exon 17 and causing a frameshift mutation was identi®ed in two independently ascertained families. RT ± PCR and longrange DNA PCR were employed to characterize the rearrangement that was ®nally shown to be the result of a recombination between two very similar Alu repeats. This type of mutation is not identi®ed by the conventional methods of mutation detection which are based on PCR ampli®cation of single exons. Therefore, further search for gene rearrangements is needed to better de®ne the proportion of`high risk' families that might be explained by gross genomic alterations of the BRCA1 gene.

In this randomized study, we found no difference in sensitivity between DTT and sonication for the detection of PJI, and both of those tests were more sensitive than standard tissue cultures. Thus, cultures of sonication or DTT fluid should be considered important additional tools to standard cultures for definition of PJI and should be considered together with other criteria, especially in settings where infection is not suspected before revision surgery.Level of Evidence Level I, diagnostic study.