Editor—Linkage data suggest thatBRCA1 and BRCA2gene alterations account for the majority of hereditary breast/ovarian cancer cases.1 Though comprehensive screening of theBRCA1 gene has been attempted on a number of occasions, only two thirds of expected mutations have been detected so far.1-3 Most efforts have relied on standard PCR techniques, including direct sequencing, single strand conformation polymorphism (SSCP) analysis, heteroduplex analysis (HDA), denaturing gradient gel electrophoresis (DGGE), and protein truncation testing (PTT), with a focus on point and small mutations.2 The relatively low rate of detection of BRCA1gene mutations may be because of the existence of large rearrangements, which are not detected by such approaches. Supporting this hypothesis, a number of large rearrangements, ranging from 0.5 to 23.8 kb and spanning the entire BRCA1 gene, have recently been detected by Southern blotting, analysis ofBRCA1 lymphocyte transcripts, and long range PCR.4-14 In most cases, the characterised rearrangements are the result of unequal recombination events between Alu sequences, which cover 41.5% of BRCA1introns.15

Here we report the identification, using colour bar coding on combed DNA, of a previously undescribed large rearrangement of theBRCA1 gene in an American breast/ovarian cancer family with ancestors from France and Germany (fig1).