RESUMO
Lynch syndrome is an autosomal dominant disorder due to mutations in DNA mismatch repair genes, causing young onset colorectal cancer and extra-colonic cancers such as endometrial and stomach cancers. We genotyped MLH1 and MSH2 in patients suspected to have Lynch syndrome and correlated patient clinical characteristics and family history with deleterious mutations. Eighty-five unrelated patients participated. Comprehensive sequencing was performed for MLH1 and MSH2, including all coding regions, splice-site junctions and promoter regions. Of the 29 different mutations found, 11 were deleterious, of which 10 were in MLH1 and 1 in MSH2. Three recurring MLH1 deleterious mutations were found in two unrelated Chinese patients each, and haplotype analysis suggested common ancestral origin for the recurring mutations and possible founder effect. Families with clinical diagnosis of HNPCC (i.e. family history which fulfills the Amsterdam I/II criteria) was the strongest predictor for finding a deleterious mutation, and stomach cancer was the most commonly reported extra-colonic cancer in families found with a deleterious MLH1 or MSH2 mutation. The observation of recurring deleterious MLH1 mutations in our study suggests possible founder effect and may have implications on genetic testing in Asia.
