Premutations of the fragile-X (FRAXA) gene were thought to have no clinical effects until recent reports of an increased incidence of premature ovarian failure in females and a late-onset neurological disorder in males.
A significant association of familial POF and FRAXA premutation carriers with POF having low copy of the (TA)n polymorphism as compared to controls was observed.
First, the couples have to be informative (the number of triplet repeats on the healthy FMR-1 allele of the mother has to be different from the number of repeats on the healthy FMR-1 allele of the father) and second, women with a premutation are at increased risk of premature ovarian failure.