Association of FMR1 repeat size with ovarian dysfunction.
BACKGROUND
Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk.


METHODS
Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes.


CONCLUSIONS
We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (> or =100 repeats).
Sullivan
A K
AK
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Marcus
M
M
Epstein
M P
MP
Allen
E G
EG
Anido
A E
AE
Paquin
J J
JJ
Yadav-Shah
M
M
Sherman
S L
SL
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D004303:Dosage Compensation, Genetic; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D051860:Fragile X Messenger Ribonucleoprotein 1; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D018392:Genomic Imprinting; D006801:Humans; D008594:Menopause, Premature / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015995:Prevalence; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology* / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors
D005640:Follicle Stimulating Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human