Preliminary evidence of genetic anticipation in XXXX .

@entity1 @entity309 @entity29 @entity2743
Despite strong epidemiologic evidence in favor of a genetic component in the etiology of @entity2743 , few hereditary risk factors have been consistently identified. The term genetic anticipation denotes a decrease in the age of onset as disease is passed through generations. In the past 5 years, genetic anticipation has been described in immune-mediated diseases such as @entity309 and chronic @entity29 , and recently this phenomenon has been linked to unstable expanded trinucleotide repeat sequences in several diseases. If present in @entity2743 , anticipation could provide clues to its genetic etiology. The aim of the present study was to investigate whether genetic anticipation may occur in @entity2743 . Age at diagnosis and age at ascertainment were registered and compared in 33 same-gender parent-offspring pairs with @entity2743 from multiply affected families primarily ascertained for a genetic linkage study. The mean age at diagnosis was 46.6 years (range, 16-77) in the parents and 34.1 years (range, 16-44) in the @entity1 . The difference in the mean age at diagnosis between parents and their @entity1 was 12.5 years (95% confidence interval 3.0-21.9), p = 0.010. @entity1 were younger than their parents at diagnosis in 25 of 33 pairs (76%). In 7 pairs (21%), the parent was diagnosed after the @entity1 according to the calendar years. Essentially similar results were obtained after controlling for gender and smoking habits. In conclusion, our data suggest that @entity1 in the second affected generation seem to acquire their disease at an earlier time in life in familial cases of @entity2743 , indicating that genetic anticipation might occur.
