Detection of exon deletions and duplications of the mismatch repair genes in hereditary nonpolyposis colorectal cancer families using multiplex polymerase chain reaction of short fluorescent fragments

Large genomic deletions within the mismatch repair MLH1 and MSH2 genes have been identified in families with the hereditary nonpolyposis colorectal ca ncer (HNPCC) syndrome, and their detection represents a technical problem, To facilitate their detection, we developed a simple semiquantitative proce dure based on the multiplex PCR of short fluorescent fragments. This method allowed us to confirm in HNPCC families three known deletions of MLH1 or M SH2 and to detect in 19 HNPCC families, in which analysis of mismatch repai r genes using classical methods had revealed no alteration, a deletion of e xon 5 and a duplication of MSH2 involving exons 9 and 10. The presence of s uch duplications, the frequency of which is probably underestimated, must b e considered in HNPCC families in which conventional screening methods have failed to detect mutations.