ClinVar

In affected members of 2 generations of an Ohio family with HNPCC (120435), Pyatt et al. (2003) identified a genomic deletion of approximately 11.4 kb encompassing the first 2 exons of the MSH2 gene. By Southern blot analysis, using a cDNA probe spanning the first 7 exons of MSH2, an alteration in each of 3 different enzyme digests was observed (including a unique 13-kb band on Hind III digests), which suggested the presence of a large alteration in the 5-prime region of the gene. The authors then generated mouse-human cell hybrids from a mutation carrier which contained a single copy each of human chromosome 2, upon which the MSH2 gene resides. Southern blots of DNA from the cell hybrids demonstrated the same unique 13-kb band from 1 MSH2 allele, as seen in the diploid DNA. DNA from this same monosomal cell hybrid failed to amplify in PCR using primers to exons 1 and 2, demonstrating the deletion of these sequences in 1 MSH2 allele, and the breakpoints involving Alu repeats were identified by PCR amplification and sequence analysis.