New hMLH1 and hMSH2 gene mutations in families with hereditary non-polyposis colorectal cancer (HNPCC)

Two families with hereditary non-polyposis colorectal cancer (HNPCC) were studied for mutations in the mismatch repair genes, hMLH1 and hMSH2. The entire coding regions of both genes were analysed by PCR-TGGE and -DGGE and subsequent sequencing of abnormal products. In one of the families a deletion of two adenosine nucleotides in codon 64 in exon 2 of hMLH1 was found that results in a stop codon at amino acid position 75. The second family showed a deletion of 6 nucleotides at position Val100-Glu101 in exon 2 of the hMSH2 gene. Interestingly, the mutation in hMLH1 caused only carcinomas of the colon (Lynch I), whereas the hMSH2 deletion led to a wide spectrum of cancers (Lynch II).