A novel MSH2 mutation in a Chinese family with hereditary non-polyposis colorectal cancer.

Objective: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary colon cancer syndrome accounting for 1-5% of all colorectal cancer cases. Germline mutations in DNA mismatch repair (MMR) genes are associated with the clinical phenotype of HNPCC. Defects in the MSH2 gene may account for about 40% of HNPCC cases including nucleotide substitutions, deletions and insertions. Only a few mutations were reported in Chinese families. This study was performed to identify the disease-causing gene mutation(s) and conduct pre-symptomatic diagnosis in a Chinese family with HNPCC.

Methods: Mutation analysis in MLH1 and MSH2 followed by pre-symptomatic diagnosis in MSH2 was performed on genomic DNA isolated from the family members.

Results: A novel duplication mutation of four nucleotides in exon 7 of MSH2 (MSH2: c.1216_1219dupCGAC) resulting in a premature stop 10 codons downstream in MSH2 (p.L407fsX417) was found. The mutation was associated with HNPCC and an asymptomatic carrier was found in the family.

Conclusions: HNPCC in a Chinese family is associated with a novel mutation in the MSH2 gene (MSH2: c.1216_1219dupCGAC).