Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?
Most examples of hereditary non-polyposis cancer syndrome (Lynch syndrome), including the Muir-Torre syndrome, are associated with microsatellite instability (MSI) and germline mutations in mismatch repair genes-most commonly MLH1 or MSH2.
Muir-Torre syndrome is usually inherited in an autosomal dominant fashion and associated with mutations in the mismatch repair genes, predominantly in MLH1 and MSH2 genes.
Four (44%) of nine families with MLH1 mutations had a member with Muir-Torre syndrome compared with 10 (42%) of 24 families with MSH2 mutations (P = .302).
We did not detect any correlation between clinical phenotype and the genetic linkage results, but a Muir-Torre syndrome family excluded from linkage to hMLH1 was likely to be linked to hMSH2 and showed microsatellite instability in a tumour from an affected relative.
Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas.
Evidence indicating microsatellite stability in three of 17 patients with a clinical history indicative of Muir-Torre syndrome and a mutation in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs from that of MLH-1 and MSH-2 mutations and further supports the use of immunohistochemistry as a screening tool in patients with Muir-Torre syndrome with an extended panel that includes MSH-6.