Expansion of the FMR-1 CGG repeat in Ontario fragile X kindreds

As a major provider of molecular analysis of the FMR-1 CGG repeat sequence in the province of Ontario, we have ascertained 120 families positive for an expansion of the FMR-1 CGG repeat sequence. An analysis of expanded FMR-1 alleles in 239 individuals from 60 kindreds was done. We observed a significant negative correlation between repeat size and age in both male and female carriers (females: -0.437, p<0.0001 males; -0.302, p<0.001). Evidence of mitotic instability was observed in 75% of individuals who carry more than 200 CGG repeats. The maximum number of major alleles that could be distinguished in any one individual was seven. If the lowest allele size present was compared amongst all individuals and so on to the lagest size, then a stepwise increase in repeat size from the lowest repeat to the largest was observed.