TRUNCATED HMSH2 TRANSCRIPT OCCURS AS A COMMON VARIANT IN THE POPULATION - IMPLICATIONS FOR GENETIC DIAGNOSIS

Germline mutations of the hMSH2 gene are responsible for many cases of hereditary nonpolyposis colorectal cancer, While screening for hMSH2 gene mutations in hereditary nonpolyposis colorectal cancer kindreds, we observed that a previously reported germline mutation is in fact a common, alternatively spliced variant in the population. Using RT-PCR and the protein truncation test, the hMSH2 exon 13 deletion variant wa s found in more than 90% of individuals. The exon 13 deletion transcri pt was only present in lymphocyte RNA, no abnormalities were detected in genomic DNA flanking exon 13, and the deletion transcript is appare ntly not translated. These findings highlight further that caution sho uld be exercised in providing genetic risk assessment on the basis of currently used germline mutation detection strategies.