Molecular Characterization of FMR1 Gene by TP-PCR in Women of Reproductive Age and Women with Premature Ovarian Insufficiency.

BACKGROUND

Fragile X syndrome is caused by CGG repeat expansion mutation in the FMR1 gene. Normal alleles have 5-44 CGG repeats with AGG interruptions. The expanded gray zone (GZ) (45-54 repeats) and premutation (PM) (55-200 repeats) alleles are often uninterrupted and are unstably inherited in subsequent generations. The prevalence of PM and GZ carriers is high in the female population, at 1/66 and 1/113, respectively, and PM is associated with fertility problems in 20% of cases.

OBJECTIVE

Our objective was to molecularly characterize CGG repeats and AGG interruption sequences in the FMR1 gene in women of reproductive age and in women with premature ovarian insufficiency (POI).

MATERIALS AND

METHODS

We conducted molecular analysis of the FMR1 gene from 300 women of reproductive age and 140 women with POI using triplet primed-polymerase chain reaction. This enabled us to identify carriers and to document CGG repeat size and the AGG interruption pattern.

RESULTS

In women of reproductive age, 1.7% were GZ carriers and 0.3% were PM carriers; in women with POI, 3.6% were GZ carriers and 2.14% were PM carriers. The frequency of GZ and PM carriers did not significantly differ between the cohorts (Fisher's exact test: p < 2.23 for GZ vs. control and p < 0.101 for PM vs. control). Carriers received genetic counselling; family screening identified an additional seven carriers.

CONCLUSION

We documented preliminary data on the prevalence of GZ and PM carriers among the studied cohorts. The identification of PM carriers among women with POI serves a dual purpose of recognizing a cause for ovarian dysfunction and enabling genetic counselling, which will help carriers when making reproductive decisions.