Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency.
Genetics in Medicine
Nature Publishing Group
This work is licensed under a Creative Commons Attribution Unported 3.0 License. To view a copy of this license, visit http:// creativecommons.org/licenses/by/3.0/deed.en_US
Purpose:Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR1 expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published.Methods:We studied FMR1 CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55-200 CGG repeats) and intermediate (45-54 CGG repeats) alleles in women with primary ovarian insufficiency (n = 254) and early menopause (n = 1,881).Results:The prevalence of the premutation was 2.0% in primary ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = 1.7-17.4; P = 0.004) for primary ovarian insufficiency and 2.0 (95% confidence interval = 0.8-5.1; P = 0.12) for early menopause. Combining primary ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = 1.02-5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or primary ovarian insufficiency.Conclusion:FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of primary ovarian insufficiency and early menopause.Genet Med advance online publication 23 May 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.64.
Breakthrough Breast Cancer
The Institute of Cancer Research
Sir John Fisher Foundation
addresses: University of Exeter Medical School, University of Exeter St Luke's, Exeter, UK.
This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.
Genetics in Medicine, 2013, 16 (1) p19-24