Probable involvement of a germ-line mutation of an unknown mismatch repairgene in a Japanese Muir-Torre syndrome phenotype

A combination of haplotype analysis and direct sequencing were conducted on Japanese Muir-Torre syndrome kindred. In the kindred, two females revealed a hereditary non-polyposis colon cancer (HNPCC) phenotype and one male had a sebaceous tumor in addition to a HNPCC phenotype. Haplotype analysis and direct sequencing failed to show involvement of the known mismatch repair genes, with the exception of MSH5, in this kindred. Analysis of large fragm ents (from 3.9 to 6.2 kb) covering the entire 25 kb MSH5 gene in the proban d revealed the absence of gross changes in the promoter region and exons. T he direct sequencing of the promoter region and all 25 exons failed to demo nstrate any mutations in the coding regions except for a CA repeat polymorp hism in intron 3 and a C/A polymorphism in intron 15. Taken together presen t results indicate that a novel and yet unknown mismatch repair gene is lik ely involved in the HNPCC in this kindred. (C) 2000 Elsevier Science Irelan d Ltd. All rights reserved.