NOVEL ALLELE OF THE HMLH1 GENE BEARING A TTC DELETION IN THE 3'-UNTRANSLATED REGION

SSCP analysis of the hMLH1 gene in two kindreds affected by hereditary nonpolyposis colorectal cancer (HNPCC) revealed the presence of uniqu e conformers in all patients affected by colorectal cancer. Sequence a nalysis of the corresponding region of the gene revealed a 3 base pair s deletion within a TTC tandem repeat (G TTC TCC T-->G TTC T) beginnin g 29 base pairs downstream of the termination codon of the gene in the 3' untranslated region. This deletion causes the loss of an MboII res triction site. Analysis extended to 113 healthy unrelated individuals and 27 unrelated HNPCC patients demonstrated the occurrence of this no vel variant of the hMLH1 gene at similar frequencies in unrelated HNPC C patients (3.7%) and in control individuals (2.2%). The allele bearin g the TTC deletion appears to be expressed at levels comparable to tho se of the wild-type allele.