Article

Examination of reproductive aging milestones among women who carry the FMR1 premutation.

Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322, USA.
Human Reproduction (Impact Factor: 4.67). 09/2007; 22(8):2142-52. DOI: 10.1093/humrep/dem148
Source: PubMed

ABSTRACT The fragile X premutation is characterized by a large CGG repeat track (55-199 repeats) in the 5' UTR of the FMR1 gene. This X-linked mutation leads to an increased risk for premature ovarian failure; interestingly, the association of repeat size with risk is non-linear. We hypothesize that the premutation-associated ovarian insufficiency is due to a diminished oocyte pool and examined reproductive aging milestones by repeat size group to determine if the same non-linear association is observed.
We analyzed cross-sectional reproductive history questionnaire data from 948 women with a wide range of repeat sizes.
We have confirmed the non-linear relationship among premutation carriers for ovarian insufficiency. The mid-range repeat size group (80-100 repeats), not the highest group, had an increased risk for: altered cycle traits (shortened cycle length, irregular cycles and skipped cycles), subfertility and dizygotic twinning. Smoking, a modifiable risk, decreased the reproductive lifespan of women with the premutation by about 1 year, similar to its effect on non-carriers. As expected, premutation carriers were found to be at an increased risk for osteoporosis.
Possible molecular mechanisms to explain the non-linear repeat size risk for ovarian insufficiency are discussed.

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