FMR1 CGG expansions: prevalence and sex ratios.

ABSTRACT

We have estimated the prevalence of FMR1 premutation and gray zone CGG repeat expansions in a population-based sample of 19,996 male and female adults in Wisconsin and compared the observed sex ratios of the prevalence of FMR1 CGG premutation and gray zone expansions to theoretical sex ratios. The female premutation prevalence was 1 in 148 and comparable to past research, but the male premutation prevalence of 1 in 290 is somewhat higher than most previous estimates. The femalemale premutation prevalence ratio is in line with the theoretically predicted sex ratio. The prevalence of CGG repeats in the gray zone (45-54 repeats) was 1 in 33 females and 1 in 62 males. The prevalence of the "expanded" gray zone (defined here as 41-54 CGG repeats) was 1 in 14 females and 1 in 22 males, leading to a femalemale ratio of 1.62 (95% confidence interval 1.39-1.90). This femalemale ratio was significantly lower than the expected ratio of 2.0. We examined results from three previously published FMR1 prevalence studies and found similar femalemale ratios for CGG repeats in this "expanded" gray zone range (pooled femalemale ratio across all four studies 1.66, 95% confidence interval 1.51-1.82). Further research is needed to understand the apparent excess prevalence of males with CGG repeats in this range.