BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease due to germline mutations of human mismatch repair genes, mainly hMLH1 and hMSH2. The aim of the present study was to identify the point mutations and large genomic deletions of hMLH1 and hMSH2 genes in 14 Chinese HNPCC families. METHODS: Fourteen families fulfilling the Chinese HNPCC criteria were involved in this study. Genomic DNA isolated from peripheral blood samples was analyzed. Point mutations were detected by denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing. Multiplex polymerase chain reaction and GeneScan analysis were employed to detect the large genomic deletions of these two genes. RESULTS: Four of the 14 probands (29%) had sequence abnormalities that probably affect the protein function in the exonic regions of hMLH1 and hMSH2 genes. Included were one complete deletion of exons 1-7 and one missense mutation of the hMSH2 gene, and one nonsense mutation and one missense mutation of the hMLH1 gene. The large genomic deletion accounted for 25% (one out of four) of all mutations. Half (two out of four, 50%) of the mutations were missense mutation. In addition, one silent mutation, four polymorphisms in the exonic regions and four polymorphisms in the intronic regions were also discovered. CONCLUSIONS: Point mutations and large genomic deletions of the hMLH1 and hMSH2 genes were responsible for nearly one-third of Chinese HNPCC families. Detection of large genomic deletions should be involved in the routine screening manual for HNPCC families.
BACKGROUND:Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease due to germline mutations of human mismatch repair genes, mainly hMLH1 and hMSH2. The aim of the present study was to identify the point mutations and large genomic deletions of hMLH1 and hMSH2 genes in 14 Chinese HNPCC families. METHODS: Fourteen families fulfilling the Chinese HNPCC criteria were involved in this study. Genomic DNA isolated from peripheral blood samples was analyzed. Point mutations were detected by denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing. Multiplex polymerase chain reaction and GeneScan analysis were employed to detect the large genomic deletions of these two genes. RESULTS: Four of the 14 probands (29%) had sequence abnormalities that probably affect the protein function in the exonic regions of hMLH1 and hMSH2 genes. Included were one complete deletion of exons 1-7 and one missense mutation of the hMSH2 gene, and one nonsense mutation and one missense mutation of the hMLH1 gene. The large genomic deletion accounted for 25% (one out of four) of all mutations. Half (two out of four, 50%) of the mutations were missense mutation. In addition, one silent mutation, four polymorphisms in the exonic regions and four polymorphisms in the intronic regions were also discovered. CONCLUSIONS: Point mutations and large genomic deletions of the hMLH1 and hMSH2 genes were responsible for nearly one-third of Chinese HNPCC families. Detection of large genomic deletions should be involved in the routine screening manual for HNPCC families.