Implications of the FMR1 gene in menopause:: study of 147 Spanish women

Objective: To evaluate the relationship between the FMR1 premutation and premature ovarian failure (POF) in the Spanish population and the possible incorporation of this test in gynecological procedures for women with POF or early menopause (EM). Design: Clinical and molecular genetic study. Ninety-eight premutated and six full-mutated carriers of fragile X syndrome and 43 women with POF were studied by polymerase chain reaction and Southern blot analysis for the CGG repeat expansion in the FMR1 gene. Results: Among premutated carriers, 12.2% ( 12 of 98) presented with POF, and 15.3% (15 of 98) presented with EM. Neither POF nor EM was observed in any of the six full-mutated women. Two women of 43 from the POF population (4.65%) were carriers for the CGG premutation in the FMR1 gene. No correlation between CGG expansion size and age at menopause was found. A biased paternal origin of the premutation and a high twinning incidence was found in all premutated women, whether they had POF or not. Conclusions: Our data support the hypothesis that the FMR1 gene is one of the genes associated with POF and EM. Analysis of the CGG expansion in the FMR1 gene may be justified in women with POF and EM until the real role of the FMR1 premutation is determined.