Role for genetic anticipation in XXXX .

@entity1 @entity4309 @entity5 @entity179 @entity14 @entity4310
PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in @entity179 , whereas its role in @entity4310 is unclear. We assessed anticipation in @entity4309 ( @entity14 [ @entity14 ]), in which DNA mismatch repair (MMR) defects cause early and accelerated @entity5 development with a broad @entity5 spectrum. @entity1 AND METHODS: In the population-based Danish @entity14 registry, 407 MMR gene mutation carriers who had developed @entity5 associated with @entity4309 , were identified. These individuals formed 290 parent- @entity1 pairs in which age at the first @entity5 diagnosis was assessed. A paired t-test and a specifically developed bivariate model were used to assess a possible role of anticipation. RESULTS: Both methods revealed anticipation with @entity1 developing @entity5 mean 9.8 years (P < .001) earlier than parents using the paired t-test and 5.5 years (P < .001) earlier using the bivariate model. Birth cohort effects were excluded since anticipation with 7.2 years earlier age at onset was identified also in the oldest cohort, in which the @entity1 were observed until they were older than 80 years. The effect remained when @entity5 diagnosed at surveillance were excluded, applied to maternal as well as paternal inheritance, and was independent of the MMR gene mutated. CONCLUSION: The effect from anticipation demonstrated in this large, population-based @entity4309 cohort underscores the need to initiate surveillance programs at young age. It should also stimulate research into the genetic mechanisms that determine age at onset and whether the genetic instability that characterizes @entity4309 can be linked to anticipation.
