Hypermethylation of the MLH1 promoter has been shown to cause MSI and be a cause of mismatch repair deficiency [48], so a methylation-specific multiplex ligation probe amplification (MLPA) assay from MRC Holland (Product no. ME011-B3/Amsterdam, the Netherlands) was included as a test option (validation data not shown) [49]. The gene discussed is MLH1; the disease is mismatch repair cancer syndrome 1.