Premature ovarian failure (POF) and fragile X premutation females: From POF to fragile X carrier identification, from fragile X carrier diagnosis to POF association data

Abstract

Early menopause in the fragile X carriers has been well documented in several reports. All surveys demonstrated that 13-25% of fragile X carriers experienced premature ovarian failure (POF), defined as menopause before the age of 40 years. In 1995 we started screening two groups of subjects as a part of a Fragile X Research Program: 1) women previously diagnosed as fragile X carriers from the register of our center and 2) women with POF and without a family history of fragile X or other forms of mental retardation. In this study we report the preliminary data collected from 75 fragile X families; in 30 of them, POF was present in one or several subjects, all of whom had a fragile X premutation. None of the women with a full mutation experienced POF in our series of patients. We also identified 89 families without a family history of fragile X or mental retardation, and there were 108 subjects who experienced POF, of which 6.5% had a fragile X premutation. This is 70-fold higher than the background prevalence of fragile X premutation in the Italian population and suggests an association with POF. These data confirm the results of other surveys.

Identification of fragile X pre-mutation carriers in the Chinese obstetric population using a robust FMR1 polymerase chain reaction assay: implications for screening and prenatal diagnosis

“…In addition, pre-mutation carriers are at risk of developing fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS) in late adult life, although they are mentally normal. 5,6 Intermediate alleles are repeat numbers between 45 and 54, and individuals carrying theses alleles are at risk of expanding into pre-mutation but not into full mutation. [7][8][9] Because of the significant morbidity associated with FXS, and since most maternal carriers are clinically silent during their reproductive years, many experts have put forward the notion of preconception or prenatal fragile X carrier screening for females.…”

Number of CGG repeats in the FMR1 gene of Japanese patients with primary ovarian insufficiency

“…Ishizuka frequency of FMR1 premutations among Japanese patients with POI. The frequency of premutation carriers among women with the sporadic form of POI ranges between 1.6% and 3.3% (27,(28)(29)(30)(31) in Caucasian populations, and one study has described a frequency of 4.8% in a group of screened Slovenian patients (32). A study of 80 Indian patients with POI revealed that none of them had CGG repeats within the premutation range (33).…”

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

“…Women with premutation level repeats in this gene are at increased risk of premature ovarian failure, [1][2][3] alternatively termed primary ovarian insufficiency. Some reports have suggested that women with 35 to 44 CGGs, 4,5 35 to 54 CGGs, 6 and <28 CGG repeat lengths 7 may be associated with less severe ovarian dysfunction, often manifest as diminished ovarian reserve.…”