@entity4309 ( XXXX ) diagnostics.

@entity1 @entity6756 @entity124 @entity4309 @entity5 @entity4311 @entity14437 @entity8554 @entity14 @entity817 @entity4638
BACKGROUND: Preventive programs for individuals who have high lifetime risks of @entity14 may reduce disease morbidity and mortality. Thus, it is important to identify the factors that are associated with @entity14 and to monitor the effects of tailored surveillance. In particular, @entity1 with @entity4309 , @entity14 ( @entity14 ), have an increased risk to develop @entity14 at an early age. The syndrome is explained by germline mutations in DNA mismatch repair (MMR) genes, and there is a need for diagnostic tools to preselect @entity1 for genetic testing to diagnose those with @entity14 . METHODS: @entity1 (n = 112) from 285 families who were counseled between 1990 and 2005 at a clinic for @entity1 at high risk for @entity14 were selected for screening to detect mutations in MMR genes @entity6756 , @entity4311 , @entity4638 , and @entity14437 based on family history, @entity124 ( @entity124 ), and immunohistochemical analysis of MMR protein expression. @entity5 were also screened for @entity817 @entity8554 mutations; @entity1 with the mutation were considered as non- @entity14 . RESULTS: Among the 112 @entity1 who were selected for screening, 69 had germline MMR mutations (58 pathogenic and 11 of unknown biologic relevance). Sixteen of the 69 mutations (23%) were missense mutations. Among @entity1 with @entity5 , pathogenic MMR mutations were found in 38 of 43 (88%) of @entity1 in families who met Amsterdam criteria and in 13 of 22 (59%) of @entity1 in families who did not. Among @entity1 with @entity5 , pathogenic MMR mutations were found in 5 of 17 (29%) of families meeting Amsterdam criteria and in 1 of 30 (3%) of non-Amsterdam families with one @entity1 younger than age 50 years. In three @entity1 with @entity5 who had pathogenic mutations in @entity6756 or @entity4638 , immunohistochemistry showed loss of the mutated protein. CONCLUSION: Our findings suggest that missense MMR gene mutations are common in @entity14 and that germline MMR mutations are also found in @entity1 with @entity5 .
