ABSTRACT
<p><b>OBJECTIVE</b>Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary colon cancer syndromes accounting for 1%-5% of all colorectal cancer cases. Germline mutations in at least five genes coding for DNA mismatch repair (MMR) proteins are associated with the clinical phenotype of HNPCC. More than 400 MMR mutations have been identified in HNPCC patients, and about 40% of mutations affect MSH2 gene including nucleotide substitutions, deletions, and insertions. Only a few mutations have been reported in Chinese families.</p><p><b>METHODS</b>A Chinese family with HNPCC was collected and peripheral blood of individuals from the family was obtained. Mutation analysis was performed on genomic DNA.</p><p><b>RESULTS</b>The family fulfilled Amsterdam criteria I, and 17 people out of 31 were diagnosed as malignant tumor for 21 times. Twelve people (70.6%) had rectal cancer, and the onset age was young with an average of 42.9 years old. Right side colon cancer was common in the family. A novel duplication mutation of four nucleotides in exon 7 MSH2 (MSH2: c.1215_1218dupCCGA) was found, which result in a premature stop 10 codons downstream in MSH2 (p.L407fsX417) in the family. Site-specific PCR was applied to the pre-symptomatic diagnosis.</p><p><b>CONCLUSION</b>This novel genomic mutation MSH2 was confirmed to be pathogenic, and polymerase chain reaction with modified primer was successfully applied to the pre-symptomatic diagnosis. These data expand the spectrum MSH2 mutations causing HNPCC.</p>